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Fu P, Zhang M, Bai L, Chen S, Chen W, Li Z, Yue J, Dong C, Li R. Intestinal Bacterial Dysbiosis and Liver Fibrosis in Mice Through Gut-Liver Axis and NLRP3 Inflammatory Pathway Caused by Fine Particulate Matter. J Appl Toxicol 2025. [PMID: 39979029 DOI: 10.1002/jat.4767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 02/01/2025] [Accepted: 02/09/2025] [Indexed: 02/22/2025]
Abstract
Fine particulate matter (PM2.5) is associated with risks of liver diseases and intestinal bacterial dysbiosis, in which the gut-liver axis regulation mechanisms induced by PM2.5 exposure are still limited so far. In this study, after 12 weeks of exposure to atmospheric PM2.5 (64 μg/m3) and clean air in winter in Taiyuan, China, we collected liver and intestinal tissues and serum in male mice to perform toxicology experiments. The results showed that PM2.5 significantly exacerbated the pathological injury in the liver and intestine and liver fibrosis in mice, along with elevated levels of pro-inflammatory cytokines and lipopolysaccharide (LPS) levels in the serum. PM2.5 caused abnormal liver function and activated TLR4/NF-κB/NLRP3 pathway in mouse liver. PM2.5 also significantly inhibited the expression of intestinal mucosal tight junction proteins such as ZO-1 and occludin. Besides, from 16S rRNA gene sequencing results in intestinal and fecal samples, we found that PM2.5 decreased the diversity and abundance of intestinal bacteria, along with reducing Shannon, Chao1 and Ace indices and increasing Simpson indices. Principal component analysis (PCA) showed that mice's intestinal bacterial composition and β-diversity in the PM2.5-exposed group significantly differed from the control group. KEGG pathway analyzed key functional genes and metabolic pathways in important mouse bacterial communities in the PM2.5-exposed group. It suggested that PM2.5 exposure exacerbates liver fibrosis in mice via the NLRP3 pathway. PM2.5 caused intestinal mucosal injury, intestinal bacterial disorders and increased LPS levels, leading to the activation of inflammatory pathways, which can exacerbate liver fibrosis via the gut-liver axis.
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Affiliation(s)
- Pengfei Fu
- Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China
- Faculty of Health, York University, Toronto, Canada
| | - Mei Zhang
- Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China
| | - Lirong Bai
- Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China
| | - Shanshan Chen
- Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China
| | - Wenqi Chen
- Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China
| | - Zhiping Li
- Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China
| | - Jianwei Yue
- Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China
| | - Chuan Dong
- Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China
- Institute of Judicial Identification Techniques for Environmental Damage of Shanxi University-Unisdom, Taiyuan, China
| | - Ruijin Li
- Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China
- Institute of Judicial Identification Techniques for Environmental Damage of Shanxi University-Unisdom, Taiyuan, China
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Zhao Y, Peng Y, Wang M, Zhao Y, He Y, Zhang L, Liu J, Zheng S. Exposure to PM 2.5 and its constituents is associated with metabolic dysfunction-associated fatty liver disease: a cohort study in Northwest of China. ENVIRONMENTAL GEOCHEMISTRY AND HEALTH 2024; 46:304. [PMID: 39002087 DOI: 10.1007/s10653-024-02071-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 06/06/2024] [Indexed: 07/15/2024]
Abstract
Accumulating animal studies have demonstrated associations between ambient air pollution (AP) and metabolic dysfunction-associated fatty liver disease (MAFLD), but relevant epidemiological evidence is limited. We evaluated the association of long-term exposure to AP with the risk of incident MAFLD in Northwest China. The average AP concentration between baseline and follow-up was used to assess individual exposure levels. Cox proportional hazard models and restricted cubic spline functions (RCS) were used to estimate the association of PM2.5 and its constituents with the risk of MAFLD and the dose-response relationship. Quantile g-computation was used to assess the joint effects of mixed exposure to air pollutants on MAFLD and the weights of the various pollutants. We observed 1516 cases of new-onset MAFLD, with an incidence of 10.89%. Increased exposure to pollutants was significantly associated with increased odds of MAFLD, with hazard ratios (HRs) of 2.93 (95% CI: 1.22, 7.00), 2.86 (1.44, 5.66), 7.55 (3.39, 16.84), 4.83 (1.89, 12.38), 3.35 (1.35, 8.34), 1.89 (1.02, 1.62) for each interquartile range increase in PM2.5, SO42-, NO3-, NH4+, OM, and BC, respectively. Stratified analyses suggested that females, frequent exercisers and never-drinkers were more susceptible to MAFLD associated with ambient PM2.5 and its constituents. Mixed exposure to SO42-, NO3-, NH4+, OM and BC was associated with an increased risk of MAFLD, and the weight of BC had the strongest effect on MAFLD. Exposure to ambient PM2.5 and its constituents increased the risk of MAFLD.
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Affiliation(s)
- Yamin Zhao
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Yindi Peng
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Minzhen Wang
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, China.
| | - Yanan Zhao
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Yingqian He
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Lulu Zhang
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Jing Liu
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Shan Zheng
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, China.
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Peng J, Wang S, Wang Y, Yu W, Zha Y, Gao S. Effects of ozone exposure on lipid metabolism in Huh-7 human hepatoma cells. Front Public Health 2023; 11:1222762. [PMID: 37521985 PMCID: PMC10374329 DOI: 10.3389/fpubh.2023.1222762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 06/19/2023] [Indexed: 08/01/2023] Open
Abstract
Ozone pollution is a major environmental concern. According to recent epidemiological studies, ozone exposure increases the risk of metabolic liver disease. However, studies on the mechanisms underlying the effects of ozone exposure on hepatic oxidative damage, lipid synthesis, and catabolism are limited. In this study, Huh-7 human hepatocellular carcinoma cells were randomly divided into five groups and exposed to 200 ppb O3 for 0, 1, 2, 4, and 8 h. We measured the levels of oxidative stress and analyzed the changes in molecules related to lipid metabolism. The levels of oxidative stress were found to be significantly elevated in Huh-7 hepatocellular carcinoma cells after O3 exposure. Moreover, the expression levels of intracellular lipid synthases, including SREBP1, FASN, SCD1, and ACC1, were enhanced. Lipolytic enzymes, including ATGL and HSL, and the mitochondrial fatty acid oxidase, CPT1α, were inhibited after O3 exposure. In addition, short O3 exposure enhanced the expression of the intracellular peroxisomal fatty acid β-oxidase, ACOX1; however, its expression decreased adaptively with longer exposure times. Overall, O3 exposure induces an increase in intracellular oxidative stress and disrupts the normal metabolism of lipids in hepatocytes, leading to intracellular lipid accumulation.
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Affiliation(s)
- Jianhao Peng
- College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, China
| | - Siyuan Wang
- College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, China
| | - Yunlong Wang
- College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, China
| | - Wanchao Yu
- College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, China
| | - Yejun Zha
- Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Beijing, China
| | - Shuxin Gao
- College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, China
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Wirsching J, Nagel G, Tsai MY, de Hoogh K, Jaensch A, Anwander B, Sokhi RS, Ulmer H, Zitt E, Concin H, Brunekreef B, Hoek G, Weinmayr G. Exposure to ambient air pollution and elevated blood levels of gamma-glutamyl transferase in a large Austrian cohort. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 883:163658. [PMID: 37100134 DOI: 10.1016/j.scitotenv.2023.163658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/05/2023] [Accepted: 04/18/2023] [Indexed: 05/07/2023]
Abstract
Gamma glutamyl transferase (GGT) is related to oxidative stress and an indicator for liver damage. We investigated the association between air pollution and GGT in a large Austrian cohort (N = 116,109) to better understand how air pollution affects human health. Data come from voluntary prevention visits that were routinely collected within the Vorarlberg Health Monitoring and Prevention Program (VHM&PP). Recruitment was ongoing from 1985 to 2005. Blood was drawn and GGT measured centralized in two laboratories. Land use regression models were applied to estimate individuals' exposure at their home address for particulate matter (PM) with a diameter of <2.5 μm (PM2.5), <10 μm (PM10), fraction between 10 μm and 2.5 μm (PMcoarse), as well as PM2.5 absorbance (PM2.5abs), NO2, NOx and eight components of PM. Linear regression models, adjusting for relevant individual and community-level confounders were calculated. The study population was 56 % female with a mean age of 42 years and mean GGT was 19.0 units. Individual PM2.5 and NO2 exposures were essentially below European limit values of 25 and 40 μg/m3, respectively, with means of 13.58 μg/m3 for PM2.5 and 19.93 μg/m3 for NO2. Positive associations were observed for PM2.5, PM10, PM2.5abs, NO2, NOx, and Cu, K, S in PM2.5 and PM10 fractions and Zn mainly in PM2.5 fraction. The strongest association per interquartile range observed was an increase of serum GGT concentration by 1.40 % (95 %-CI: 0.85 %; 1.95 %) per 45.7 ng/m3 S in PM2.5. Associations were robust to adjustments for other biomarkers, in two-pollutant models and the subset with a stable residential history. We found that long-term exposure to air pollution (PM2.5, PM10, PM2.5abs, NO2, NOx) as well as certain elements, were positively associated with baseline GGT levels. The elements associated suggest a role of traffic emissions, long range transport and wood burning.
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Affiliation(s)
- Jan Wirsching
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
| | - Gabriele Nagel
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany; Agency for Preventive and Social Medicine, Bregenz (aks), Austria
| | - Ming-Yi Tsai
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
| | - Kees de Hoogh
- Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland
| | - Andrea Jaensch
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
| | - Bernhard Anwander
- Institut für Umwelt und Lebensmittelsicherheit des Landes Vorarlberg, Bregenz, Austria
| | - Ranjeet S Sokhi
- Centre for Atmospheric and Climate Physics Research (CACP), School of Physics, Astronomy and Mathematics, University of Hertfordshire, Hatfield, UK
| | - Hanno Ulmer
- Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria
| | - Emanuel Zitt
- Agency for Preventive and Social Medicine, Bregenz (aks), Austria; Department of Internal Medicine 3, LKH Feldkirch, Feldkirch, Austria
| | - Hans Concin
- Agency for Preventive and Social Medicine, Bregenz (aks), Austria
| | - Bert Brunekreef
- Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Gerard Hoek
- Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
| | - Gudrun Weinmayr
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
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Li FR, Liao J, Zhu B, Li X, Cheng Z, Jin C, Mo C, Wu X, Li Q, Liang F. Long-term exposure to air pollution and incident non-alcoholic fatty liver disease and cirrhosis: A cohort study. Liver Int 2023; 43:299-307. [PMID: 36069651 DOI: 10.1111/liv.15416] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 08/09/2022] [Accepted: 09/05/2022] [Indexed: 01/25/2023]
Abstract
BACKGROUND AND AIMS Epidemiological evidence regarding the association of air pollution with the risk of non-alcoholic fatty liver disease (NAFLD) is limited. This study was to examine the associations of long-term exposure to various air pollutants and overall air pollution with risk of incident NAFLD as well as cirrhosis, a major liver-related morbidity for NAFLD. METHODS Included were 456 687 UK residents. Air pollution data included PM2.5 , PM2.5-10 , PM10 , NO2 and NOx . A weighted air pollution score was also generated from PM10 and NOx . Cox proportional hazard models were employed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS We identified 4978 cases of NAFLD and 1575 cases of incident cirrhosis, over a median follow-up of 11.9 years. PM2.5 , PM10 , NO2 and NOx exposures contributed to the excess risk of NAFLD associated with air pollution score; and the corresponding adjusted HRs (95% CI) were 1.10 (1.05, 1.14), 1.14 (1.09, 1.20), 1.19 (1.13, 1.24) and 1.11 (1.07, 1.15), respectively, for each interquartile range increase in the above specific air pollutants. Similar patterns were also indicated for cirrhosis risk. Alcohol consumption was an effect modifier for the association between air pollution score and NAFLD risk, whereas body mass index modified the association for cirrhosis risk. CONCLUSION Long-term exposure to air pollution was associated with risks of NAFLD and cirrhosis among the UK population.
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Affiliation(s)
- Fu-Rong Li
- Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Jian Liao
- School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China
| | - Bin Zhu
- School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China
| | - Xia Li
- School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China
| | - Zhiyuan Cheng
- School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China
| | - Cheng Jin
- School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China
| | - Chunbao Mo
- School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China
| | - Xianbo Wu
- School of Public Health, Southern Medical University, Guangzhou, China
| | - Qian Li
- School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China
| | - Fengchao Liang
- Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China
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Wang MW, Sun L, Wen W, Wang J, Wang CY, Ni J, Jiang JJ, Feng ZH, Cheng YR. Explore the Relationship Between Short-Term Ambient Air Pollution Exposure and Daily Outpatient Visits for Metabolic Related Fatty Liver. Risk Manag Healthc Policy 2022; 15:1751-1759. [PMID: 36157290 PMCID: PMC9505349 DOI: 10.2147/rmhp.s364270] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 08/15/2022] [Indexed: 12/03/2022] Open
Abstract
Background Many studies have shown that the pollution of fine particles in the air is related to the incidence of chronic diseases. However, research on air pollution and metabolism-associated fatty liver disease (MAFLD) is limited. Objective The purpose of this study was to explore the relationship between short-term ambient air pollution and daily outpatient visits for metabolic-related fatty liver. Methods We used a quasi-Poisson regression generalized additive model to stratify analyses by season, age, and gender. Results From January 1, 2017, to August 31, 2019, 10,562 confirmed MAFLD outpatient visits were recorded. A 10 µg/m3 increase of fine particular matter (PM10and PM2.5) and NO2 concentrations corresponding with percent change were 0.82 (95% confidence interval [CI], 0.49–1.15), 0.57 (95% CI, 0.18–0.98), and 0.86 (95% CI, 0.59–1.13) elevation in MAFLD outpatient visits. In terms of season, the impact estimates of NO2 and PM2.5% change were 3.55 (95% CI, 1.23–5.87) and 1.12 (95% CI, 0.78–1.46) in the hot season and transition season, respectively. Compared with the warm season, the impact estimates of PM10were more significant in the cool season: 2.88 (95% CI, 0.66–5.10). NO2 has the greatest effect in the transition season, whereas PM10 has the greatest highest effect in the cool and hot seasons. Compared with other pollutants, PM2.5 has the greatest impact in the age stratification, which percent change are 2.69 (95% CI, 0.77–5.61) and 2.88 (95% CI, 0.37–6.40) respectively. The impact values of PM2.5 in male and female percent change were 3.60 (95% CI, 0.63–6.57) and 1.65 (95% CI, 1.05–2.25), respectively. Conclusion This study shows that the air pollutants are related to the number of outpatient visits for MAFLD. The effects of different air pollutants on MAFLD outpatient visits were different by season, ages, and gender.
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Affiliation(s)
- Ming-Wei Wang
- Metabolic Disease Center, Affiliated Hospital of Hangzhou Normal University, Hangzhou, People's Republic of China
| | - Lixia Sun
- Zhejiang University of Water Resources and Electric Power, Hangzhou, People's Republic of China
| | - Wen Wen
- Metabolic Disease Center, Affiliated Hospital of Hangzhou Normal University, Hangzhou, People's Republic of China
| | - Jie Wang
- Hangzhou Zhenqi Technology Co., Ltd, Hangzhou, People's Republic of China
| | - Chun-Yi Wang
- Metabolic Disease Center, Affiliated Hospital of Hangzhou Normal University, Hangzhou, People's Republic of China
| | - Jie Ni
- Metabolic Disease Center, Affiliated Hospital of Hangzhou Normal University, Hangzhou, People's Republic of China
| | - Jing-Jie Jiang
- Metabolic Disease Center, Affiliated Hospital of Hangzhou Normal University, Hangzhou, People's Republic of China
| | - Zhan-Hui Feng
- Neurological Department, Affiliated Hospital of Guizhou Medical University, Guiyang, People's Republic of China
| | - Yong-Ran Cheng
- School of Public Health, Hangzhou Medical College, Hangzhou, People's Republic of China
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Chin WS, Pan SC, Huang CC, Chen PJ, Guo YL. Exposure to Air Pollution and Survival in Follow-Up after Hepatocellular Carcinoma. Liver Cancer 2022; 11:474-482. [PMID: 36158593 PMCID: PMC9485987 DOI: 10.1159/000525346] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 05/09/2022] [Indexed: 02/04/2023] Open
Abstract
Introduction Air pollutants are classified as carcinogens by the International Agency for Research on Cancer. Long-term exposure to ambient particulate matter with an aerodiameter of 2.5 μm or lower (PM2.5) has been reported to be linked with increased mortality due to hepatocellular carcinoma (HCC). However, the effects of air pollutants other than PM2.5 on HCC-related mortality have not been fully investigated. Accordingly, we conducted this study to assess the effect of long-term exposure to air pollutants (PM2.5 and nitrogen dioxide [NO2]) on HCC-related mortality. Method In 2005, the Taiwan Liver Cancer Network (TLCN) was established by the National Research Program for Genomic Medicine to recruit liver cancer patients from 5 major medical centers in northern, central, and southern Taiwan. The TLCN had successfully recruited 9,344 patients by the end of 2018. In this study, we included 1,000 patients randomly sampled from the TLCN to assess the effect of exposure to air pollutants on HCC mortality after HCC diagnosis. Daily averages of PM2.5 and NO2 concentrations were retrieved from 77 air quality-monitoring stations and interpolated to the townships of patients' residences by using the Kriging method. The effect of air pollutants on HCC survival was assessed using a Cox proportional hazards model. Results A total of 940 patients were included in the analysis. After adjusting for potential confounders and mutually adjusting for co-pollutants, we observed that the hazards ratio (95% confidence interval) for HCC-related mortality for every 1-μg/m3 increase in PM2.5 concentration was 1.11 (1.08-1.14) and that for every 1-ppb increase in NO2 concentration was 1.08 (1.03-1.13). Conclusion Our study suggests that long-term exposure to PM2.5 and NO2 was associated with decreased survival time in patients with HCC in Taiwan.
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Affiliation(s)
- Wei-Shan Chin
- School of Nursing, College of Medicine, National Taiwan University (NTU) and NTU Hospital, Taipei, Taiwan
| | - Shin-Chun Pan
- National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
| | - Ching-Chun Huang
- Department of Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine and NTU Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Graduate Institute of Microbiology, NTU College of Medicine, Taipei, Taiwan
- Department of Gastroenterology, NTU Hospital, Taipei, Taiwan
| | - Yue Leon Guo
- National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
- Department of Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine and NTU Hospital, Taipei, Taiwan
- Institute of Environmental and Occupational Health Sciences, National Taiwan University College of Public Health, Taipei, Taiwan
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Fanaei H, Mard SA, Sarkaki A, Goudarzi G, Khorsandi L. Gallic acid protects the liver against NAFLD induced by dust exposure and high-fat diet through inhibiting oxidative stress and repressing the inflammatory signaling pathways NF-kβ/TNF-α/IL-6 in Wistar rats. AVICENNA JOURNAL OF PHYTOMEDICINE 2021; 11:527-540. [PMID: 34745924 PMCID: PMC8554286 DOI: 10.22038/ajp.2021.17835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 08/24/2020] [Accepted: 08/24/2020] [Indexed: 12/03/2022]
Abstract
Objective: The burden of diseases and death related to environmental pollution is becoming a major public health challenge. This study was designed to evaluate the deleterious effects of a combination of dust exposure and high-fat diet on liver function. Gallic acid as a potent antioxidant was used to prevent/alleviate non-alcoholic fatty liver disease (NAFLD) in rats exposed to dust and HFD. Materials and Methods: 24 rats were randomly divided into 3 experimental groups: HFD+Clean air, HFD+N/S+Dust and HFD+gallic acid+Dust. Animals were exposed to CA/ dust for six weeks on alternate days. At the end of the experiments, rats were anesthetized and samples were taken to perform molecular, biomedical, and histopathological evaluations. Results: Dust exposure induced NAFLD features in rats under HFD. Dust exposure and HFD disrupted liver enzymes and lipid profile. Dust exposure and HFD increased liver MDA level, mRNA expression of NF-Kβ, TNF-α, IL-6, Nrf2, HO1 and miRs122, and 34a. Dust+HFD also decreased liver total antioxidant capacity level. Pretreatment with GA improved almost studied variables in the HFD+GA+Dust group. Conclusion: The present study showed that HFD given for 6 weeks and dust exposure induced NAFLD in Wistar rats through inducing oxidative stress. Oxidative stress through activating the inflammatory pathways caused NAFLD features. GA pretreatment by inhibiting oxidative stress, effectively protected liver functions against HFD+Dust induced inflammation.
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Affiliation(s)
- Hafseh Fanaei
- Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyyed Ali Mard
- Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Alireza Sarkaki
- Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Gholamreza Goudarzi
- Air Pollution and Respiratory Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Environmental Technologies Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Layasadat Khorsandi
- Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Department of Anatomical Sciences, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Iran
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9
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Garcia E, Stratakis N, Valvi D, Maitre L, Varo N, Aasvang GM, Andrusaityte S, Basagana X, Casas M, de Castro M, Fossati S, Grazuleviciene R, Heude B, Hoek G, Krog NH, McEachan R, Nieuwenhuijsen M, Roumeliotaki T, Slama R, Urquiza J, Vafeiadi M, Vos MB, Wright J, Conti DV, Berhane K, Vrijheid M, McConnell R, Chatzi L. Prenatal and childhood exposure to air pollution and traffic and the risk of liver injury in European children. Environ Epidemiol 2021; 5:e153. [PMID: 34131614 PMCID: PMC8196121 DOI: 10.1097/ee9.0000000000000153] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 03/25/2021] [Indexed: 11/26/2022] Open
Abstract
Nonalcoholic fatty liver disease is the most prevalent pediatric chronic liver disease. Experimental studies suggest effects of air pollution and traffic exposure on liver injury. We present the first large-scale human study to evaluate associations of prenatal and childhood air pollution and traffic exposure with liver injury. METHODS Study population included 1,102 children from the Human Early Life Exposome project. Established liver injury biomarkers, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and cytokeratin-18, were measured in serum between ages 6-10 years. Air pollutant exposures included nitrogen dioxide, particulate matter <10 μm (PM10), and <2.5 μm. Traffic measures included traffic density on nearest road, traffic load in 100-m buffer, and inverse distance to nearest road. Exposure assignments were made to residential address during pregnancy (prenatal) and residential and school addresses in year preceding follow-up (childhood). Childhood indoor air pollutant exposures were also examined. Generalized additive models were fitted adjusting for confounders. Interactions by sex and overweight/obese status were examined. RESULTS Prenatal and childhood exposures to air pollution and traffic were not associated with child liver injury biomarkers. There was a significant interaction between prenatal ambient PM10 and overweight/obese status for alanine aminotransferase, with stronger associations among children who were overweight/obese. There was no evidence of interaction with sex. CONCLUSION This study found no evidence for associations between prenatal or childhood air pollution or traffic exposure with liver injury biomarkers in children. Findings suggest PM10 associations maybe higher in children who are overweight/obese, consistent with the multiple-hits hypothesis for nonalcoholic fatty liver disease pathogenesis.
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Affiliation(s)
- Erika Garcia
- Department of Preventive Medicine, University of Southern California, Los Angeles, CA
| | - Nikos Stratakis
- Department of Preventive Medicine, University of Southern California, Los Angeles, CA
| | - Damaskini Valvi
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Léa Maitre
- NA, ISGlobal, Universitat Pompeu Fabra (UPF), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Nerea Varo
- Clinical Biochemistry Department, Clínica Universidad de Navarra, Pamplona, Spain
| | - Gunn Marit Aasvang
- Department of Environmental Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Sandra Andrusaityte
- Department of Environmental Sciences, Vytautas Magnus University, Kaunas, Lithuania
| | - Xavier Basagana
- NA, ISGlobal, Universitat Pompeu Fabra (UPF), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Maribel Casas
- NA, ISGlobal, Universitat Pompeu Fabra (UPF), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Montserrat de Castro
- NA, ISGlobal, Universitat Pompeu Fabra (UPF), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Serena Fossati
- NA, ISGlobal, Universitat Pompeu Fabra (UPF), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | | | - Barbara Heude
- NA, Université de Paris, Centre for Research in Epidemiology and Statistics (CRESS), INSERM, INRAE, Paris, France
| | - Gerard Hoek
- Department Population Health Sciences, Utrecht University, Utrecht, Netherlands
| | - Norun Hjertager Krog
- Department of Environmental Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Rosemary McEachan
- Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom
| | - Mark Nieuwenhuijsen
- NA, ISGlobal, Universitat Pompeu Fabra (UPF), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Theano Roumeliotaki
- Department of Social Medicine, University of Crete, Heraklion, Crete, Greece
| | - Rémy Slama
- Department of Prevention and Treatment of Chronic Diseases, Institute for Advanced Biosciences (IAB), INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France
| | - Jose Urquiza
- NA, ISGlobal, Universitat Pompeu Fabra (UPF), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Marina Vafeiadi
- Department of Social Medicine, University of Crete, Heraklion, Crete, Greece
| | - Miriam B. Vos
- Department of Pediatrics, Emory University, Atlanta, GA
| | - John Wright
- Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom
| | - David V. Conti
- Department of Preventive Medicine, University of Southern California, Los Angeles, CA
| | - Kiros Berhane
- Department of Biostatistics, Columbia University, New York, NY
| | - Martine Vrijheid
- NA, ISGlobal, Universitat Pompeu Fabra (UPF), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Rob McConnell
- Department of Preventive Medicine, University of Southern California, Los Angeles, CA
| | - Lida Chatzi
- Department of Preventive Medicine, University of Southern California, Los Angeles, CA
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10
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Juanola O, Martínez-López S, Francés R, Gómez-Hurtado I. Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18105227. [PMID: 34069012 PMCID: PMC8155932 DOI: 10.3390/ijerph18105227] [Citation(s) in RCA: 146] [Impact Index Per Article: 36.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 04/29/2021] [Accepted: 05/09/2021] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of chronic liver disease in the Western world, probably due to the growing prevalence of obesity, metabolic diseases, and exposure to some environmental agents. In certain patients, simple hepatic steatosis can progress to non-alcoholic steatohepatitis (NASH), which can sometimes lead to liver cirrhosis and its complications including hepatocellular carcinoma. Understanding the mechanisms that cause the progression of NAFLD to NASH is crucial to be able to control the advancement of the disease. The main hypothesis considers that it is due to multiple factors that act together on genetically predisposed subjects to suffer from NAFLD including insulin resistance, nutritional factors, gut microbiota, and genetic and epigenetic factors. In this article, we will discuss the epidemiology of NAFLD, and we overview several topics that influence the development of the disease from simple steatosis to liver cirrhosis and its possible complications.
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Affiliation(s)
- Oriol Juanola
- Gastroenterology and Hepatology, Translational Research Laboratory, Ente Ospedaliero Cantonale, Università della Svizzera Italiana, 6900 Lugano, Switzerland
| | - Sebastián Martínez-López
- Clinical Medicine Department, Miguel Hernández University, 03550 San Juan de Alicante, Spain
- Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario de Alicante, 03010 Alicante, Spain
| | - Rubén Francés
- Clinical Medicine Department, Miguel Hernández University, 03550 San Juan de Alicante, Spain
- Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario de Alicante, 03010 Alicante, Spain
- Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, 28029 Madrid, Spain
| | - Isabel Gómez-Hurtado
- Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario de Alicante, 03010 Alicante, Spain
- Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, 28029 Madrid, Spain
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11
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Doherty Lyons S, Blum JL, Hoffman-Budde C, Tijerina PB, Fiel MI, Conklin DJ, Gany F, Odin JA, Zelikoff JT. Prenatal Exposure to Gutkha, a Globally Relevant Smokeless Tobacco Product, Induces Hepatic Changes in Adult Mice. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17217895. [PMID: 33126512 PMCID: PMC7662769 DOI: 10.3390/ijerph17217895] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 10/07/2020] [Accepted: 10/15/2020] [Indexed: 12/16/2022]
Abstract
Maternal exposures during pregnancy affect the onset and progression of adult diseases in the offspring. A prior mouse study indicated that maternal tobacco smoke exposure affects hepatic fibrosis in adult offspring. Gutkha, a broadly used smokeless tobacco (ST) product, is widely used by pregnant woman in many countries. The objective of this murine study was to evaluate whether oral maternal exposure to gutkha during pregnancy alters non-alcoholic fatty liver disease (NAFLD) in adult offspring: risk factors for the progression of NAFLD to cirrhosis in adults remain elusive. Buccal cavity 'painting' of pregnant mice with gutkha began on gestational days (GD) 2-4 and continued until parturition. Beginning at 12 weeks of age, a subset of offspring were transitioned to a high-fat diet (HFD). Results demonstrated that prenatal exposure to gutkha followed by an HFD in adulthood significantly increased the histologic evidence of fatty liver disease only in adult male offspring. Changes in hepatic fibrosis-related cytokines (interleukin (IL)-1b and IL-6) and in hepatic collagen mRNA expression were observed when comparing adult male offspring exposed to gutkha in utero to those not exposed. These findings indicate that maternal use of gutkha during pregnancy affects NAFLD in adult offspring in a sex-dependent manner.
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Affiliation(s)
- Shannon Doherty Lyons
- Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA; (S.D.L.); (J.L.B.); (C.H.-B.); (P.B.T.)
| | - Jason L. Blum
- Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA; (S.D.L.); (J.L.B.); (C.H.-B.); (P.B.T.)
- Product Safety Labs, Dayton, NJ 08810, USA
| | - Carol Hoffman-Budde
- Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA; (S.D.L.); (J.L.B.); (C.H.-B.); (P.B.T.)
| | - Pamela B. Tijerina
- Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA; (S.D.L.); (J.L.B.); (C.H.-B.); (P.B.T.)
| | - M. Isabel Fiel
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;
| | - Daniel J. Conklin
- American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, Kentucky, KY 40202, USA;
| | - Francesca Gany
- Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA;
| | - Joseph A. Odin
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Correspondence: (J.A.O.); (J.T.Z.)
| | - Judith T. Zelikoff
- Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA; (S.D.L.); (J.L.B.); (C.H.-B.); (P.B.T.)
- Correspondence: (J.A.O.); (J.T.Z.)
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12
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Wang M, Tan J, Zhou J, Yi B, Huang Z. Farnesoid X receptor mediates hepatic steatosis induced by PM 2.5. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:34412-34420. [PMID: 32557026 DOI: 10.1007/s11356-020-09676-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 06/09/2020] [Indexed: 06/11/2023]
Abstract
Ambient particulate matter (PM) newly has been regarded as a conceivable hazard for public health. A large number of studies have described that PM, exceptionally PM2.5, is correlated with respiratory, cardiovascular, and metabolic diseases, etc. PM2.5-induced hepatocyte steatosis previously has been uncovered both in cellular and murine models. Nevertheless, less is known about the underlying mechanism. Here, we found that PM2.5 could cause the downregulation of farnesoid X receptor (FXR), a key transcription factor for lipid metabolism. FXR could regulate the accumulation of lipid droplets induced by PM2.5 in vitro. Moreover, FXR-/- mice were exposed to PM2.5 for 2 months to investigate the role of FXR in pathogenesis of PM2.5-induced hepatic steatosis in vivo. The results showed that exposure of wild-type (WT) mice to PM2.5 caused mild liver steatosis compared with the mice exposure to filtered air (FA). Furthermore, the content of triglyceride (TG) and total cholesterol (TC) was elevated in WT mice liver triggered by the inhalation of PM2.5. However, there was no statistical difference in TG and TC content between FXR-/- mice with and without PM2.5 exposure. Overall, our finding suggested FXR mediated PM2.5-induced hepatic steatosis.
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Affiliation(s)
- Mengyao Wang
- Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Jieqiong Tan
- Center for Medical Genetics, Life Science School, Central South University, Changsha, 410013, China
| | - Ji Zhou
- Typhoon Institute/CMA, Shanghai Key Laboratory of Meteorology and Health, Shanghai, 200030, China
| | - Bin Yi
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Zhijun Huang
- Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
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13
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A cohort study on long-term exposure to air pollution and incidence of liver cirrhosis. Environ Epidemiol 2020; 4:e109. [PMID: 33778350 PMCID: PMC7941789 DOI: 10.1097/ee9.0000000000000109] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 07/08/2020] [Indexed: 01/06/2023] Open
Abstract
Cirrhosis is an advanced liver disease affecting millions of people worldwide, involving high healthcare costs. Despite experimental evidence suggesting a possible role of airborne pollutants in liver diseases, epidemiological studies are lacking. We aimed at investigating the association between exposure to air pollutants and incidence of cirrhosis in a large population-based cohort in Rome. Methods We used an administrative cohort established from the 2001 census. We included all adults of 30 years of age or older who were free of cirrhosis, resulting in a study population of over 1.2 million subjects. Follow-up of the subjects ended on 31 December 2015. We ascertained incident cases of cirrhosis from regional mortality and hospital discharge registries using a validated algorithm. We assessed exposure of the subjects to PM10, PM coarse, PM2.5, PM2.5 absorbance, NO2, NOx, and PM metal components at their residential address using Land Use Regression models. We used Cox regression models, adjusted for relevant covariates, to estimate the association between air pollution exposure and cirrhosis incidence. Results We observed 10,111 incident cases of cirrhosis, with a crude incidence rate of 67 × 100,000 person-years. Long-term exposure to all pollutants tested was significantly associated with cirrhosis, e.g., PM10 (hazard ratios [HR], 1.05; 95% confidence interval [CI], 1.01-1.09, per 10 µg/m3 increments), PM coarse (HR, 1.11; 95% CI, 1.05-1.17, per 10 µg/m3 increments), PM2.5 (HR, 1.08; 95% CI, 1.03-1.13, per 5 µg/m3 increments), and NO2 (HR, 1.03; 95% CI, 1.02-1.05, per 10 µg/m3 increments). The associations were robust in secondary analyses. Conclusions Our findings suggest a possible contribution of air pollution to the development of cirrhosis.
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14
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Lin SY, Yang YC, Chang CYY, Lin CC, Hsu WH, Ju SW, Hsu CY, Kao CH. Risk of Polycystic Ovary Syndrome in Women Exposed to Fine Air Pollutants and Acidic Gases: A Nationwide Cohort Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16234816. [PMID: 31801197 PMCID: PMC6926786 DOI: 10.3390/ijerph16234816] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 11/26/2019] [Accepted: 11/28/2019] [Indexed: 12/17/2022]
Abstract
Background: Air pollutants cause endocrine disorders and hormone disruption. The relationship between air pollutants and polycystic ovary syndrome (PCOS) must be carefully investigated using a nationwide cohort. Methods: Data were extracted from two nationwide databases, namely Longitudinal Health Insurance Database and Taiwan Air Quality Monitoring Database, and analyzed. The study considered a range of data that began on 1 January 2000 and ended on 31 December 2013. Women diagnosed with PCOS were excluded. From the residential data, the study assessed the daily concentrations of sulfur dioxide (SO2), nitrogen oxides (NOx), nitrogen monoxide (NO), nitrogen dioxide (NO2), and PM2.5 the women were exposed to. A Cox proportional hazard regression model was applied to assess PCOS risk. Results: In total, 91,803 women were enrolled in this study; of those women, 2072 developed PCOS after 12 years of follow-up. The mean daily concentrations of SO2, NOx, NO, NO2, and PM2.5 women were exposed to were 4.25 (±1.44) ppb, 20.41 (±6.65) ppb, 9.25 (±4.36) ppb, 20.99 (±3.33) ppb, and 30.85 (±6.16) μg/m3, respectively. Compared with the first-quartile levels of exposure, the fourth-quartile levels of exposure to SO2, NOx, NO, NO2, and PM2.5 increased PCOS risk by 10.31 times (95% CI = 8.35–12.7), 3.37 times (95% CI = 2.86–3.96), 4.18 times (95% CI = 3.57–4.89), 7.46 times (95% CI = 6.38–8.71), and 3.56 times (95% CI = 3.05–4.15), respectively. Conclusion: Women exposed to a high concentrations of air pollutants, namely SO2, NO, NO2, NOx, and PM2.5, had a high PCOS risk.
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Affiliation(s)
- Shih-Yi Lin
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 40447, Taiwan; (S.-Y.L.); (C.Y.-Y.C.); (C.-C.L.); (W.-H.H.); (S.-W.J.); (C.-Y.H.)
- Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung 40402, Taiwan
| | - Yu-Cih Yang
- Management Office for Health Data, China Medical University Hospital, Taichung 40402, Taiwan;
- College of Medicine, China Medical University, Taichung 40402, Taiwan
| | - Cherry Yin-Yi Chang
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 40447, Taiwan; (S.-Y.L.); (C.Y.-Y.C.); (C.-C.L.); (W.-H.H.); (S.-W.J.); (C.-Y.H.)
- Department of Gynecology, China Medical University Hospital, Taichung 40402, Taiwan
| | - Cheng-Chieh Lin
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 40447, Taiwan; (S.-Y.L.); (C.Y.-Y.C.); (C.-C.L.); (W.-H.H.); (S.-W.J.); (C.-Y.H.)
- Department of Family Medicine, China Medical University Hospital, Taichung 40402, Taiwan
| | - Wu-Huei Hsu
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 40447, Taiwan; (S.-Y.L.); (C.Y.-Y.C.); (C.-C.L.); (W.-H.H.); (S.-W.J.); (C.-Y.H.)
- Department of Chest Medicine, China Medical University Hospital, Taichung 40402, Taiwan
| | - Shu-Woei Ju
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 40447, Taiwan; (S.-Y.L.); (C.Y.-Y.C.); (C.-C.L.); (W.-H.H.); (S.-W.J.); (C.-Y.H.)
- Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung 40402, Taiwan
| | - Chung-Y. Hsu
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 40447, Taiwan; (S.-Y.L.); (C.Y.-Y.C.); (C.-C.L.); (W.-H.H.); (S.-W.J.); (C.-Y.H.)
| | - Chia-Hung Kao
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 40447, Taiwan; (S.-Y.L.); (C.Y.-Y.C.); (C.-C.L.); (W.-H.H.); (S.-W.J.); (C.-Y.H.)
- Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung 40402, Taiwan
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung, 40402, Taiwan
- Center of Augmented Intelligence in Healthcare, China Medical University Hospital, Taichung, 40402, Taiwan
- Correspondence: or ; Tel.: +886-4-22052121 (ext.7412); Fax: +886-4-22336174
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15
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Reyes-Caballero H, Rao X, Sun Q, Warmoes MO, Lin P, Sussan TE, Park B, Fan TWM, Maiseyeu A, Rajagopalan S, Girnun GD, Biswal S. Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice. Sci Rep 2019; 9:17423. [PMID: 31757983 PMCID: PMC6874681 DOI: 10.1038/s41598-019-53716-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 11/01/2019] [Indexed: 12/12/2022] Open
Abstract
Exposure to ambient air particulate matter (PM2.5) is well established as a risk factor for cardiovascular and pulmonary disease. Both epidemiologic and controlled exposure studies in humans and animals have demonstrated an association between air pollution exposure and metabolic disorders such as diabetes. Given the central role of the liver in peripheral glucose homeostasis, we exposed mice to filtered air or PM2.5 for 16 weeks and examined its effect on hepatic metabolic pathways using stable isotope resolved metabolomics (SIRM) following a bolus of 13C6-glucose. Livers were analyzed for the incorporation of 13C into different metabolic pools by IC-FTMS or GC-MS. The relative abundance of 13C-glycolytic intermediates was reduced, suggesting attenuated glycolysis, a feature found in diabetes. Decreased 13C-Krebs cycle intermediates suggested that PM2.5 exposure led to a reduction in the Krebs cycle capacity. In contrast to decreased glycolysis, we observed an increase in the oxidative branch of the pentose phosphate pathway and 13C incorporations suggestive of enhanced capacity for the de novo synthesis of fatty acids. To our knowledge, this is one of the first studies to examine 13C6-glucose utilization in the liver following PM2.5 exposure, prior to the onset of insulin resistance (IR).
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Affiliation(s)
- Hermes Reyes-Caballero
- Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615N. Wolfe Street, Baltimore, MD, 21205, USA.
| | - Xiaoquan Rao
- Cardiovascular Research Institute, Case Western Reserve School of Medicine, 11100 Euclid Avenue, Cleveland, OH, 44106, USA
| | - Qiushi Sun
- Department of Toxicology and Cancer Biology, Markey Cancer Center, Center for Environmental and Systems Biochemistry, University of Kentucky, 1095V.A. Drive, Lexington, KY, 40536, USA
| | - Marc O Warmoes
- Department of Toxicology and Cancer Biology, Markey Cancer Center, Center for Environmental and Systems Biochemistry, University of Kentucky, 1095V.A. Drive, Lexington, KY, 40536, USA
| | - Penghui Lin
- Department of Toxicology and Cancer Biology, Markey Cancer Center, Center for Environmental and Systems Biochemistry, University of Kentucky, 1095V.A. Drive, Lexington, KY, 40536, USA
| | - Tom E Sussan
- Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615N. Wolfe Street, Baltimore, MD, 21205, USA.,Public Health Center, Toxicology Directorate, Aberdeen Proving Ground, Aberdeen, MD, USA
| | - Bongsoo Park
- Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615N. Wolfe Street, Baltimore, MD, 21205, USA
| | - Teresa W-M Fan
- Department of Toxicology and Cancer Biology, Markey Cancer Center, Center for Environmental and Systems Biochemistry, University of Kentucky, 1095V.A. Drive, Lexington, KY, 40536, USA
| | - Andrei Maiseyeu
- Cardiovascular Research Institute, Case Western Reserve School of Medicine, 11100 Euclid Avenue, Cleveland, OH, 44106, USA
| | - Sanjay Rajagopalan
- Cardiovascular Research Institute, Case Western Reserve School of Medicine, 11100 Euclid Avenue, Cleveland, OH, 44106, USA
| | - Geoffrey D Girnun
- Department of Pharmacological Sciences, Stony Brook University, BST 8-140, Stony Brook, NY, 11794, USA.,Department of Pathology, Stony Brook University School of Medicine, Stony Brook, NY, 11794, USA
| | - Shyam Biswal
- Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615N. Wolfe Street, Baltimore, MD, 21205, USA.
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16
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Tavera Busso I, Mateos AC, González Peroni A, Graziani NS, Carreras HA. Hepatic alterations associated with fine particulate matter exposure. Toxicol Res 2019; 36:139-148. [PMID: 32257926 DOI: 10.1007/s43188-019-00014-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 06/29/2019] [Accepted: 07/29/2019] [Indexed: 10/24/2022] Open
Abstract
Several studies have pointed to fine particulate matter (PM2.5) as the main responsible for air pollution toxic effects. Indeed, PM2.5 may not only cause respiratory and cardiovascular abnormalities but it may also affect other organs such as the liver. Be that as it may, only a few studies have evaluated the PM2.5 effects on hepatic tissue. Moreover, most of them have not analyzed the relationship between particles composition and toxicological effects. In this study, healthy rats were subjected to urban levels of PM2.5 particles in order to assess their structural and functional effects on the liver. During the exposure periods, mean PM2.5 concentrations were slightly higher than the value suggested by the daily guideline of the World Health Organization. The exposed rats showed a hepatic increase of Cr, Zn, Fe, Ba, Tl and Pb levels. This group also showed leukocyte infiltration, sinusoidal dilation, hydropic inclusions and alterations in carbohydrates distribution. These histologic lesions were accompanied by serological changes, such as increase of total cholesterol and triglycerides, as well as genotoxic damage in their nuclei. We also observed significant associations between several biomarkers and PM2.5 composition. Our results show that exposure to low levels of PM2.5 might cause histologic and serological changes in liver tissue, suggesting that PM2.5 toxicity is influenced not only by their concentration but also by their composition and the exposure frequency.
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Affiliation(s)
- Iván Tavera Busso
- 1Instituto Multidisciplinario de Biología Vegetal (IMBIV), CONICET - Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, X5016GCA Córdoba, Argentina.,J. Robert Cade Foundation, Córdoba, Argentina
| | - Ana Carolina Mateos
- 1Instituto Multidisciplinario de Biología Vegetal (IMBIV), CONICET - Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, X5016GCA Córdoba, Argentina
| | - Alicia González Peroni
- 1Instituto Multidisciplinario de Biología Vegetal (IMBIV), CONICET - Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, X5016GCA Córdoba, Argentina
| | - Natalia Soledad Graziani
- 1Instituto Multidisciplinario de Biología Vegetal (IMBIV), CONICET - Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, X5016GCA Córdoba, Argentina
| | - Hebe Alejandra Carreras
- 1Instituto Multidisciplinario de Biología Vegetal (IMBIV), CONICET - Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, X5016GCA Córdoba, Argentina
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17
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Wahlang B, Jin J, Beier JI, Hardesty JE, Daly EF, Schnegelberger RD, Falkner KC, Prough RA, Kirpich IA, Cave MC. Mechanisms of Environmental Contributions to Fatty Liver Disease. Curr Environ Health Rep 2019; 6:80-94. [PMID: 31134516 PMCID: PMC6698418 DOI: 10.1007/s40572-019-00232-w] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE Fatty liver disease (FLD) affects over 25% of the global population and may lead to liver-related mortality due to cirrhosis and liver cancer. FLD caused by occupational and environmental chemical exposures is termed "toxicant-associated steatohepatitis" (TASH). The current review addresses the scientific progress made in the mechanistic understanding of TASH since its initial description in 2010. RECENT FINDINGS Recently discovered modes of actions for volatile organic compounds and persistent organic pollutants include the following: (i) the endocrine-, metabolism-, and signaling-disrupting chemical hypotheses; (ii) chemical-nutrient interactions and the "two-hit" hypothesis. These key hypotheses were then reviewed in the context of the steatosis adverse outcome pathway (AOP) proposed by the US Environmental Protection Agency. The conceptual understanding of the contribution of environmental exposures to FLD has progressed significantly. However, because this is a new research area, more studies including mechanistic human data are required to address current knowledge gaps.
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Affiliation(s)
- Banrida Wahlang
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, 40202, USA
- University of Louisville Superfund Research Center, University of Louisville, Louisville, KY, 40202, USA
| | - Jian Jin
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Juliane I Beier
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, 15213, USA
- Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA
| | - Josiah E Hardesty
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Erica F Daly
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Regina D Schnegelberger
- Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA
| | - K Cameron Falkner
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Russell A Prough
- Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Irina A Kirpich
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, 40202, USA
- Hepatobiology & Toxicology COBRE Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA
- University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY, 40202, USA
| | - Matthew C Cave
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
- University of Louisville Superfund Research Center, University of Louisville, Louisville, KY, 40202, USA.
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
- Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
- Hepatobiology & Toxicology COBRE Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
- University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY, 40202, USA.
- The Robley Rex Veterans Affairs Medical Center, Louisville, KY, 40206, USA.
- The Jewish Hospital Liver Transplant Program, Louisville, KY, 40202, USA.
- Kosair Charities Clinical & Translational Research Building, 505 South Hancock Street, Louisville, KY, 40202, USA.
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18
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Yin F, Gupta R, Vergnes L, Driscoll WS, Ricks J, Ramanathan G, Stewart JA, Shih DM, Faull KF, Beaven SW, Lusis AJ, Reue K, Rosenfeld ME, Araujo JA. Diesel Exhaust Induces Mitochondrial Dysfunction, Hyperlipidemia, and Liver Steatosis. Arterioscler Thromb Vasc Biol 2019; 39:1776-1786. [PMID: 31340670 PMCID: PMC6703953 DOI: 10.1161/atvbaha.119.312736] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 06/17/2019] [Indexed: 12/17/2022]
Abstract
OBJECTIVE Air pollution is associated with increased cardiovascular morbidity and mortality, as well as dyslipidemia and metabolic syndrome. Our goal was to dissect the mechanisms involved. Approach and Results: We assessed the effects of exposure to air pollution on lipid metabolism in mice through assessment of plasma lipids and lipoproteins, oxidized fatty acids 9-HODE (9-hydroxyoctadecadienoic) and 13-HODE (13-hydroxyoctadecadienoic), lipid, and carbohydrate metabolism. Findings were corroborated, and mechanisms were further assessed in HepG2 hepatocytes in culture. ApoE knockout mice exposed to inhaled diesel exhaust (DE, 6 h/d, 5 days/wk for 16 weeks) exhibited elevated plasma cholesterol and triglyceride levels, increased hepatic triglyceride content, and higher hepatic levels of 9-HODE and 13-HODE, as compared to control mice exposed to filtered air. A direct effect of DE exposure on hepatocytes was demonstrated by treatment of HepG2 cells with a methanol extract of DE particles followed by loading with oleic acid. As observed in vivo, this led to increased triglyceride content and significant downregulation of ACAD9 mRNA expression. Treatment of HepG2 cells with DE particles and oleic acid did not alter de novo lipogenesis but inhibited total, mitochondrial, and ATP-linked oxygen consumption rate, indicative of mitochondrial dysfunction. Treatment of isolated mitochondria, prepared from mouse liver, with DE particles and oleic acid also inhibited mitochondrial complex activity and β-oxidation. CONCLUSIONS DE exposure leads to dyslipidemia and liver steatosis in ApoE knockout mice, likely due to mitochondrial dysfunction and decreased lipid catabolism.
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Affiliation(s)
- Fen Yin
- Division of Cardiology, David Geffen School of Medicine at University of California Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA
| | - Rajat Gupta
- Division of Cardiology, David Geffen School of Medicine at University of California Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA
| | - Laurent Vergnes
- Department of Human Genetics, David Geffen School of Medicine at University of California Los Angeles, 659 Charles E. Young Drive South, Los Angeles, CA
| | | | - Jerry Ricks
- Department of Pathology, University of Washington, Seattle, WA
| | - Gajalakshmi Ramanathan
- Division of Cardiology, David Geffen School of Medicine at University of California Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA
| | - James A. Stewart
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA
| | - Diana M. Shih
- Division of Cardiology, David Geffen School of Medicine at University of California Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA
| | - Kym F. Faull
- Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior and Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California Los Angeles, 760 Westwood Boulevard, Los Angeles, CA
| | - Simon W. Beaven
- Division of Gastroenterology, David Geffen School of Medicine at University of California Los Angeles, 10833 Le Conte Avenue, CHS 44-144, Los Angeles, CA
| | - Aldons J. Lusis
- Division of Cardiology, David Geffen School of Medicine at University of California Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA
- Department of Human Genetics, David Geffen School of Medicine at University of California Los Angeles, 659 Charles E. Young Drive South, Los Angeles, CA
| | - Karen Reue
- Department of Human Genetics, David Geffen School of Medicine at University of California Los Angeles, 659 Charles E. Young Drive South, Los Angeles, CA
| | - Michael E. Rosenfeld
- Department of Pathology, University of Washington, Seattle, WA
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA
| | - Jesus A. Araujo
- Division of Cardiology, David Geffen School of Medicine at University of California Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA
- Department of Environmental Health Sciences, Fielding School of Public Health, University of California Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA
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19
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Migliaccio V, Gregorio ID, Putti R, Lionetti L. Mitochondrial Involvement in the Adaptive Response to Chronic Exposure to Environmental Pollutants and High-Fat Feeding in a Rat Liver and Testis. Cells 2019; 8:E834. [PMID: 31387296 PMCID: PMC6721750 DOI: 10.3390/cells8080834] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 07/28/2019] [Accepted: 08/03/2019] [Indexed: 02/07/2023] Open
Abstract
In our modern society, exposure to stressful environmental stimuli, such as pollutants and/or chronic high-fat feeding, continuously induce tissular/organ metabolic adaptation to promote cellular survival. In extreme conditions, cellular death and tissular/organ damage occur. Mitochondria, as a cellular energy source, seem to play an important role in facing cellular stress induced by these environmental stimuli. On the other hand, mitochondrial dysfunction and oxidative stress play a key role in environmental stress-induced metabolic diseases. However, little is known about the combined effect of simultaneous exposure to chronic high-fat feeding and environmental pollutants on metabolic alterations at a tissular and cellular level, including mitochondrial dysfunction and oxidative stress induction. Our research group recently addressed this topic by analysing the effect of chronic exposure to a non-toxic dose of the environmental pollutant dichlorodiphenyldichloroethylene (DDE) associated with high-fat feeding in male Wistar rats. In this review, we mainly summarize our recent findings on mitochondrial adaptive response and oxidative stress induction in the liver, the main tissue involved in fat metabolism and pollutant detoxification, and in male gonads, the main targets of endocrine disruption induced by both high-fat feeding and environmental pollutants.
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Affiliation(s)
- Vincenzo Migliaccio
- Department of Chemistry and Biology "Adolfo Zambelli", University of Salerno, 84084 Fisciano, Italy.
- Department of Biology, University of Naples, Federico II, 80126 Naples, Italy.
| | - Ilaria Di Gregorio
- Department of Chemistry and Biology "Adolfo Zambelli", University of Salerno, 84084 Fisciano, Italy
| | - Rosalba Putti
- Department of Biology, University of Naples, Federico II, 80126 Naples, Italy
| | - Lillà Lionetti
- Department of Chemistry and Biology "Adolfo Zambelli", University of Salerno, 84084 Fisciano, Italy.
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20
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Association of Ambient Air Pollution with Increased Liver Enzymes in Korean Adults. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16071213. [PMID: 30987355 PMCID: PMC6479611 DOI: 10.3390/ijerph16071213] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 03/22/2019] [Accepted: 03/28/2019] [Indexed: 12/14/2022]
Abstract
An association between exposure to air pollution and liver enzymes in certain areas or older people has been reported in the literature; however, it cannot be generalized to the general population. We investigated the association between air pollution, liver enzyme levels, and alcohol consumption using nationwide data of South Korean adults. Air pollutants included particulate matter with an aerodynamic diameter ≤10 µm (PM10), nitrogen dioxide (NO₂), sulfur dioxide (SO₂), and carbon monoxide (CO). Liver enzymes included alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Exposure to air pollutants were significantly associated with elevation of log ALT and log AST, especially increases from 0.0073 IU/L (95% confidence interval (CI) = 0.0042, 0.0104) to 0.0251 IU/L (95% CI = 0.0132, 0.0371) per interquartile range (IQR) increase of each pollutant (all pollutants: p < 0.001). Association of the liver enzymes with PM10 (β (95% CI) = 0.0285 IU/L (0.0201, 0.0368) for log ALT; β (95% CI) = 0.0139 IU/L (0.0079, 0.0198) for log AST) and CO (β (95% CI) = 0.0247 IU/L (0.0182, 0.0311) for log ALT; β (95% CI) = 0.0164 IU/L (0.0118, 0.0210) for log AST) were only significant among drinkers. Our findings suggest that chronic exposure to PM10 and CO is a risk factor for liver enzymes increases among the general adult population who admitted to drinking alcohol.
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21
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Ding S, Yuan C, Si B, Wang M, Da S, Bai L, Wu W. Combined effects of ambient particulate matter exposure and a high-fat diet on oxidative stress and steatohepatitis in mice. PLoS One 2019; 14:e0214680. [PMID: 30921449 PMCID: PMC6438678 DOI: 10.1371/journal.pone.0214680] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 03/18/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Chronic exposure to ambient particulate matter with aerodynamic diameters < 2.5 (PM2.5) induces oxidative injury and liver pathogenesis. The present study assessed the effect and mechanism of long-term, real-world airborne particulate matter (PM) exposure on oxidative stress and hepatic steatosis in the context of a standard chow diet (STD) and a high-fat diet (HFD); the study further explored whether a combination of PM exposure and HFD treatment exacerbates the adverse effects in mice. METHODS C57BL/6J mice fed with STD or HFD (41.26% kcal fat) were exposed to PM or filtered air (FA) for 5 months. Lipid metabolism, oxidative stress and liver pathogenesis were evaluated. Real-time PCR and western blotting were performed to determine gene expression and molecular signal transduction in liver. RESULTS Chronic airborne PM exposure impaired oxidative homeostasis, caused inflammation and induced hepatic steatosis in mice. Further investigation found that exposure to real-world PM increased the expression of hepatic Nrf2 and Nrf2-regulated antioxidant enzyme gene. The increased protein expression of the sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in the liver were also observed in PM-exposed groups. Furthermore, the combination of PM exposure and HFD treatment caused a synergistic effect on the changes of lipid accumulation oxidative stress, inflammation in the mouse liver. CONCLUSIONS Through in vivo study, we reveal that the combination of real-world ambient PM exposure and HFD treatment aggravates hepatic lipid metabolism disorders, inflammation and oxidative stress. PM exposure may accelerate the progression to non-alcoholic steatohepatitis by regulating SREBP-1c/FAS regulatory axis.
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Affiliation(s)
- Shibin Ding
- Department of nutrition and food hygiene, school of public health, Xinxiang Medical University, Xinxiang, Henan Province, PR China
- Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, PR China
- * E-mail:
| | - Chunyan Yuan
- Department of nutrition and food hygiene, school of public health, Xinxiang Medical University, Xinxiang, Henan Province, PR China
| | - Bingjie Si
- Department of nutrition and food hygiene, school of public health, Xinxiang Medical University, Xinxiang, Henan Province, PR China
| | - Mengruo Wang
- Department of nutrition and food hygiene, school of public health, Xinxiang Medical University, Xinxiang, Henan Province, PR China
| | - Shuyan Da
- Department of nutrition and food hygiene, school of public health, Xinxiang Medical University, Xinxiang, Henan Province, PR China
| | - Lanxin Bai
- Department of nutrition and food hygiene, school of public health, Xinxiang Medical University, Xinxiang, Henan Province, PR China
| | - Weidong Wu
- Department of nutrition and food hygiene, school of public health, Xinxiang Medical University, Xinxiang, Henan Province, PR China
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22
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Li R, Zhang M, Wang Y, Yung KKL, Su R, Li Z, Zhao L, Dong C, Cai Z. Effects of sub-chronic exposure to atmospheric PM 2.5 on fibrosis, inflammation, endoplasmic reticulum stress and apoptosis in the livers of rats. Toxicol Res (Camb) 2018; 7:271-282. [PMID: 30090581 PMCID: PMC6062260 DOI: 10.1039/c7tx00262a] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Accepted: 01/02/2018] [Indexed: 01/01/2023] Open
Abstract
Epidemiological studies have revealed that exposure to PM2.5 is linked to liver cancer. However, the hepatic toxicity and relevant molecular mechanisms of PM2.5 have not yet been fully described. Herein, we report on our investigation of the fibrosis, inflammation, endoplasmic reticulum (ER) stress and apoptosis in the livers of rats, caused by exposure to PM2.5 during summer and winter in Taiyuan, China. Male SD rats were sub-chronically exposed to PM2.5 (in summer: 0.2, 0.6, 1.5 mg per kg of b.w.; in winter: 0.3, 1.5, 2.7 mg per kg of b.w.) via intratracheal instillation once every 3 days for 60 days. The results showed that exposure to high dosages of PM2.5 caused the following: (1) hepatic histopathological changes and liver function decline through elevating the activities of AST, ALT, CYP450 and GST; (2) triggered liver fibrosis, in which TGF-β1, Col I, Col III, and MMP13 mRNA and protein expression were significantly upregulated, and enhanced inflammation with the overexpression of TNF-α, IL-6 and HO-1 versus the control; (3) induced liver ER stress and cell apoptosis via activating the GRP78/ATF6/CHOP/TRB3/caspase 12 pathway. The data also indicated that the liver injury induced by winter PM2.5 in Taiyuan was more serious compared to that induced by summer PM2.5. This work provides new insight into the mechanisms of PM2.5-induced liver injury, and aids the understanding of the underlying mechanisms by which PM2.5 might affect liver diseases.
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Affiliation(s)
- Ruijin Li
- Institute of Environmental Science , Institute of Biotechnology Shanxi University , Taiyuan , PR China . ; ; Tel: (+86)-351-7011011
| | - Mei Zhang
- Institute of Environmental Science , Institute of Biotechnology Shanxi University , Taiyuan , PR China . ; ; Tel: (+86)-351-7011011
| | - Ying Wang
- Institute of Environmental Science , Institute of Biotechnology Shanxi University , Taiyuan , PR China . ; ; Tel: (+86)-351-7011011
| | - Ken Kin Lam Yung
- Institute of Environmental Science , Institute of Biotechnology Shanxi University , Taiyuan , PR China . ; ; Tel: (+86)-351-7011011
- State Key Laboratory of Environmental and Biological Analysis , Department of Biology , Hong Kong Baptist University , Hong Kong SAR , China . ; ; Tel: (+852)-34117070
| | - Ruijun Su
- Institute of Environmental Science , Institute of Biotechnology Shanxi University , Taiyuan , PR China . ; ; Tel: (+86)-351-7011011
| | - Zhuoyu Li
- Institute of Environmental Science , Institute of Biotechnology Shanxi University , Taiyuan , PR China . ; ; Tel: (+86)-351-7011011
| | - Liping Zhao
- Shanxi Provincial People's Hospital , Taiyuan , PR China
| | - Chuan Dong
- Institute of Environmental Science , Institute of Biotechnology Shanxi University , Taiyuan , PR China . ; ; Tel: (+86)-351-7011011
| | - Zongwei Cai
- State Key Laboratory of Environmental and Biological Analysis , Department of Biology , Hong Kong Baptist University , Hong Kong SAR , China . ; ; Tel: (+852)-34117070
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23
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Shang Y, Sun Q. Particulate air pollution: major research methods and applications in animal models. ENVIRONMENTAL DISEASE 2018; 3:57-62. [PMID: 31549002 DOI: 10.4103/ed.ed_16_18] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Ambient air pollution is composed of a heterogeneous mixture of gaseous and solid particle compounds in which primary particles are emitted directly into the atmosphere, such as diesel soot, while secondary particles are created through physicochemical transformation. Particulate matter (PM), especially fine and ultrafine particles, can be inhaled and deposited in the alveolar cavities and penetrate into circulation. An association between high levels of air pollutants and human disease has been known for more than half a century and increasing evidences demonstrate a strong link between exposure on PM and the development of systemic diseases, such as cardiovascular and neurological disorders. Experimental animal models have been extensively used to study the underlying mechanism caused by environmental exposure to ambient PM. Due to their availability, quality, cost, and genetically modified strains, rodent models have been widely used. Some common exposure approaches include intranasal instillation, intratracheal instillation, nose-only inhalation, whole-body inhalation, and intravenous injection have been reviewed with brief summary of its performance, merit, limitation, and application. We hope this would provide useful reference in advancing experimental researches about air pollution human health and disease development.
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Affiliation(s)
- Yanan Shang
- Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio, USA
| | - Qinghua Sun
- Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio, USA.,Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio, USA.,Division of Cardiovascular Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, USA
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24
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Li W, Dorans KS, Wilker EH, Rice MB, Long MT, Schwartz J, Coull BA, Koutrakis P, Gold DR, Fox CS, Mittleman MA. Residential Proximity to Major Roadways, Fine Particulate Matter, and Hepatic Steatosis: The Framingham Heart Study. Am J Epidemiol 2017; 186:857-865. [PMID: 28605427 DOI: 10.1093/aje/kwx127] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 11/21/2016] [Indexed: 01/18/2023] Open
Abstract
We examined associations between ambient air pollution and hepatic steatosis among 2,513 participants from the Framingham (Massachusetts) Offspring Study and Third Generation Cohort who underwent a computed tomography scan (2002-2005), after excluding men who reported >21 drinks/week and women who reported >14 drinks/week. We calculated each participant's residential-based distance to a major roadway and used a spatiotemporal model to estimate the annual mean concentrations of fine particulate matter. Liver attenuation was measured by computed tomography, and liver-to-phantom ratio (LPR) was calculated. Lower values of LPR represent more liver fat. We estimated differences in continuous LPR using linear regression models and prevalence ratios for presence of hepatic steatosis (LPR ≤ 0.33) using generalized linear models, adjusting for demographics, individual and area-level measures of socioeconomic position, and clinical and lifestyle factors. Participants who lived 58 m (25th percentile) from major roadways had lower LPR (β = -0.003, 95% confidence interval: -0.006, -0.001) and higher prevalence of hepatic steatosis (prevalence ratio = 1.16, 95% confidence interval: 1.05, 1.28) than those who lived 416 m (75th percentile) away. The 2003 annual average fine particulate matter concentration was not associated with liver-fat measurements. Our findings suggest that living closer to major roadways was associated with more liver fat.
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Abu-Elmagd M, Alghamdi MA, Shamy M, Khoder MI, Costa M, Assidi M, Kadam R, Alsehli H, Gari M, Pushparaj PN, Kalamegam G, Al-Qahtani MH. Evaluation of the Effects of Airborne Particulate Matter on Bone Marrow-Mesenchymal Stem Cells (BM-MSCs): Cellular, Molecular and Systems Biological Approaches. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2017; 14:ijerph14040440. [PMID: 28425934 PMCID: PMC5409640 DOI: 10.3390/ijerph14040440] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Revised: 04/07/2017] [Accepted: 04/14/2017] [Indexed: 12/13/2022]
Abstract
Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with a range of acute and chronic diseases in humans. However, the specific effects they exert on the stem cells remain unclear. Here, we report the effects of PM collected from the city of Jeddah on proliferation, cell death, related gene expression and systems of biological analysis in bone marrow mesenchymal stem cells (BM-MSCs), with the aim of understanding the underlying mechanisms. PM2.5 and PM10 were tested in vitro at various concentrations (15 to 300 µg/mL) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM2.5 increased proliferation of BM-MSCs, while higher concentrations served to decrease it. PM10 decreased BM-MSCs proliferation in a concentration-dependent manner. The X-ray fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses demonstrated that heavy metals were associated with signaling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential expression of the apoptosis genes (BCL2, BAX); inflammation associated genes (TNF-α and IL-6) and the cell cycle regulation gene (p53). We conclude that PM causes inflammation and cell death, and thereby predisposes to chronic debilitating diseases.
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Affiliation(s)
- Muhammad Abu-Elmagd
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.
| | - Mansour A Alghamdi
- Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, P.O. Box 80208, Jeddah 21589, Saudi Arabia.
| | - Magdy Shamy
- Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, P.O. Box 80208, Jeddah 21589, Saudi Arabia.
| | - Mamdouh I Khoder
- Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, P.O. Box 80208, Jeddah 21589, Saudi Arabia.
| | - Max Costa
- New York University School of Medicine, Nelson Institute of Environmental Medicine, New York, NY 10987, USA.
| | - Mourad Assidi
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.
| | - Roaa Kadam
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.
| | - Haneen Alsehli
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.
| | - Mamdooh Gari
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.
| | - Peter Natesan Pushparaj
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.
| | - Gauthaman Kalamegam
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.
| | - Mohammed H Al-Qahtani
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.
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26
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Lin YC, Lian IB, Kor CT, Chang CC, Su PY, Chang WT, Liang YF, Su WW, Soon MS. Association between soil heavy metals and fatty liver disease in men in Taiwan: a cross sectional study. BMJ Open 2017; 7:e014215. [PMID: 28115335 PMCID: PMC5278238 DOI: 10.1136/bmjopen-2016-014215] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Metabolic factors are major risk factors for non-alcoholic fatty liver disease although other factors may also contribute to development of fatty liver disease. We explored the association between exposure to soil heavy metals and prevalence of fatty liver disease. METHODS We retrospectively analysed data from patients diagnosed with fatty liver disease in 2014 at the Health Evaluation Centre of Chang-Hua Christian Hospital (n=1137). We used residency data provided in the records of the Health Evaluation Centre and data for soil metal concentrations from a nationwide survey conducted by the Environmental Protection Administration of Taiwan. We studied the correlations between the severity of fatty liver disease and concentrations of soil heavy metals (arsenic, mercury, cadmium, chromium, copper, nickel, lead and zinc). RESULTS The prevalence of moderate to severe fatty liver disease in our study was 26.5%. Using univariate and multivariate analysis, we demonstrated that the presence of soil heavy metals was a significant risk factor for fatty liver disease in men (OR 1.83, 95% CI 1.161 to 2.899, p=0.009). With stratification by body mass index (BMI) and gender, lean men with a BMI <24 kg/m2 were the most susceptible to soil heavy metals (OR 5.059, 95% CI 1.628 to 15.728, p<0.05). CONCLUSIONS Our study suggested a significant association between exposure to soil heavy metals and fatty liver disease in lean men.
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Affiliation(s)
- Yen-Chih Lin
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Ie-Bin Lian
- Institute of Statistics and Information Science, National Changhua University of Education, Taiwan
| | - Chew-Teng Kor
- Internal Medicine Research Centre, Changhua Christian Hospital, Changhua, Taiwan
| | - Chia-Chu Chang
- Division of Nephrology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
- School of Medicine, Chung-Shan Medical University, Taichung, Taiwan
| | - Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Wan-Tzu Chang
- Institute of Statistics and Information Science, National Changhua University of Education, Taiwan
| | - Yu-Fen Liang
- Department of Health Evaluation, Changhua Christian Hospital, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
- School of Medicine, Chung-Shan Medical University, Taichung, Taiwan
| | - Maw-Soan Soon
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
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27
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Yang Z, Yan C, Liu G, Niu Y, Zhang W, Lu S, Li X, Zhang H, Ning G, Fan J, Qin L, Su Q. Plasma selenium levels and nonalcoholic fatty liver disease in Chinese adults: a cross-sectional analysis. Sci Rep 2016; 6:37288. [PMID: 27853246 PMCID: PMC5112507 DOI: 10.1038/srep37288] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Accepted: 10/28/2016] [Indexed: 11/11/2022] Open
Abstract
Selenium exposure can induce liver insulin resistance and increased liver triglyceride concentrations in animals, which may link to an increased risk of nonalcoholic fatty liver disease (NAFLD). However, epidemiological studies investigating the association between elevated plasma selenium levels and NAFLD were not available. We aimed to investigate the association of selenium levels with the prevalence of NAFLD in Chinese adults. This was a cross-sectional study of 8550 Chinese adults aged 40 yr or older in Shanghai, China. A questionnaire, anthropometric measurements, and laboratory tests were conducted. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. Plasma selenium concentration was assessed by inductively coupled plasma mass spectroscopy. The median concentration of plasma selenium was 213.0 μg/L. Elevated plasma selenium levels were associated with higher triglycerides, LDL-cholesterol, fasting plasma glucose, post-loading plasma glucose, A1c, HOMA-IR, as well as ALT, AST and γ-GT (all P < 0.05). The odds ratios were substantially higher for NAFLD (OR = 1.54, 95% CI 1.13–2.18) in the highest selenium quartile compared with those in the lowest quartile, after adjustment for potential cofounder. The results of this study provided epidemiological evidence that increased plasma selenium level is associated with elevated prevalence of NAFLD.
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Affiliation(s)
- Zhen Yang
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chonghuai Yan
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Gang Liu
- Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
| | - Yixin Niu
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiwei Zhang
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shuai Lu
- Department of Endocrinology, Xinhua Hospital Chongming Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyong Li
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongmei Zhang
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guang Ning
- Department of Endocrinology and Metabolism, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai, China
| | - Jiangao Fan
- Department of Gastroenterology, Shanghai Key Laboratory of Children's Digestion and Nutrition, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Li Qin
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of Endocrinology, Xinhua Hospital Chongming Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Su
- Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Yang J, Wei Q, Peng X, Peng X, Yuan J, Hu D. Relationship between Methyl Tertiary Butyl Ether Exposure and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study among Petrol Station Attendants in Southern China. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2016; 13:ijerph13100946. [PMID: 27669281 PMCID: PMC5086685 DOI: 10.3390/ijerph13100946] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Revised: 09/07/2016] [Accepted: 09/20/2016] [Indexed: 01/29/2023]
Abstract
Methyl tertiary butyl ether (MTBE)—A well known gasoline additive substituting for lead alkyls—causes lipid disorders and liver dysfunctions in animal models. However, whether MTBE exposure is a risk factor for non-alcoholic fatty liver disease (NAFLD) remains uncertain. We evaluate the possible relationship between MTBE exposure and the prevalence of NAFLD among 71 petrol station attendants in southern China. The personal exposure concentrations of MTBE were analyzed by Head Space Solid Phase Microextraction GC/MS. NAFLD was diagnosed by using abdominal ultrasonography according to the guidelines for the diagnosis and treatment of NAFLD suggested by the Chinese Hepatology Association. Demographic and clinical characteristics potentially associated with NAFLD were investigated. Mutivariate logistic regression analysis was applied to measure odds ratios and 95% confidence intervals (CI). The result showed that the total prevalence of NAFLD was 15.49% (11/71) among the study subjects. The average exposure concentrations of MTBE were 292.98 ± 154.90 μg/m3 and 286.64 ± 122.28 μg/m3 in NAFLD and non-NAFLD groups, respectively, and there was no statistically significant difference between them (p > 0.05). After adjusting for age, gender, physical exercise, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), white blood cell (WBC), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), the odds ratios were 1.31 (95% CI: 0.85–1.54; p > 0.05), 1.14 (95% CI: 0.81–1.32; p > 0.05), 1.52 (95% CI: 0.93–1.61; p > 0.05) in the groups (including men and women) with exposure concentrations of MTBE of 100–200 μg/m3, 200–300 μg/m3, and ≥300 μg/m3, respectively, as compared to the group (including men and women) ≤100 μg/m3. Our investigation indicates that exposure to MTBE does not seem to be a significant risk factor for the prevalence of NAFLD among petrol station attendants in southern China.
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Affiliation(s)
- Jianping Yang
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Environmental Health, School of Public Health, Southern Medical University, Guangzhou 510515, China.
- Department of Occupational Health, Baoan Center for Disease Control and Prevention of Shenzhen, Shenzhen 518100, China.
| | - Qinzhi Wei
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China.
| | - Xiaochun Peng
- South China Institute of Environmental Sciences, Ministry of Environmental Protection, Guangzhou 510655, China.
| | - Xiaowu Peng
- South China Institute of Environmental Sciences, Ministry of Environmental Protection, Guangzhou 510655, China.
| | - Jianhui Yuan
- Department of Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
| | - Dalin Hu
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Environmental Health, School of Public Health, Southern Medical University, Guangzhou 510515, China.
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Nappi F, Barrea L, Di Somma C, Savanelli MC, Muscogiuri G, Orio F, Savastano S. Endocrine Aspects of Environmental "Obesogen" Pollutants. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2016; 13:ijerph13080765. [PMID: 27483295 PMCID: PMC4997451 DOI: 10.3390/ijerph13080765] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Revised: 07/11/2016] [Accepted: 07/19/2016] [Indexed: 12/12/2022]
Abstract
Growing evidence suggests the causal link between the endocrine-disrupting chemicals (EDCs) and the global obesity epidemics, in the context in the so-called “obesogenic environment”. Dietary intake of contaminated foods and water, especially in association with unhealthy eating pattern, and inhalation of airborne pollutants represent the major sources of human exposure to EDCs. This is of particular concern in view of the potential impact of obesity on chronic non-transmissible diseases, such as type 2 diabetes, cardiovascular disease, and hormone-sensitive cancers. The key concept is the identification of adipose tissue not only as a preferential site of storage of EDCs, but also as an endocrine organ and, as such, susceptible to endocrine disruption. The timing of exposure to EDCs is critical to the outcome of that exposure, with early lifetime exposures (e.g., fetal or early postnatal) particularly detrimental because of their permanent effects on obesity later in life. Despite that the mechanisms operating in EDCs effects might vary enormously, this minireview is aimed to provide a general overview on the possible association between the pandemics of obesity and EDCs, briefly describing the endocrine mechanisms linking EDCs exposure and latent onset of obesity.
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Affiliation(s)
| | | | | | | | | | - Francesco Orio
- Department of Sports Science and Wellness, "Parthenope" University of Naples, 80133 Naples, Italy.
| | - Silvia Savastano
- Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini 5, 80131 Naples, Italy.
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Rao X, Patel P, Puett R, Rajagopalan S. Air pollution as a risk factor for type 2 diabetes. Toxicol Sci 2015; 143:231-41. [PMID: 25628401 DOI: 10.1093/toxsci/kfu250] [Citation(s) in RCA: 92] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Recent studies in both humans and animals suggest that air pollution is an important risk factor for type 2 diabetes mellitus (T2DM). However, the mechanism by which air pollution mediates propensity to diabetes is not fully understood. While a number of epidemiologic studies have shown a positive association between ambient air pollution exposure and risk for T2DM, some studies have not found such a relationship. Experimental studies in susceptible disease models do support this association and suggest the involvement of tissues involved in the pathogenesis of T2DM such as the immune system, adipose, liver, and central nervous system. This review summarizes the epidemiologic and experimental evidence between ambient outdoor air pollution and T2DM.
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Affiliation(s)
- Xiaoquan Rao
- *Division of Cardiovascular Medicine, University of Maryland, Baltimore and Maryland Institute for Applied Environmental Health, Department of Epidemiology and Biostatistics, School of Public Health, University of Maryland, College Park
| | - Priti Patel
- *Division of Cardiovascular Medicine, University of Maryland, Baltimore and Maryland Institute for Applied Environmental Health, Department of Epidemiology and Biostatistics, School of Public Health, University of Maryland, College Park
| | - Robin Puett
- *Division of Cardiovascular Medicine, University of Maryland, Baltimore and Maryland Institute for Applied Environmental Health, Department of Epidemiology and Biostatistics, School of Public Health, University of Maryland, College Park
| | - Sanjay Rajagopalan
- *Division of Cardiovascular Medicine, University of Maryland, Baltimore and Maryland Institute for Applied Environmental Health, Department of Epidemiology and Biostatistics, School of Public Health, University of Maryland, College Park
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Kim KN, Lee H, Kim JH, Jung K, Lim YH, Hong YC. Physical Activity- and Alcohol-dependent Association Between Air Pollution Exposure and Elevated Liver Enzyme Levels: An Elderly Panel Study. J Prev Med Public Health 2015; 48:151-69. [PMID: 26081652 PMCID: PMC4484281 DOI: 10.3961/jpmph.15.014] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Accepted: 04/30/2015] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES The deleterious effects of air pollution on various health outcomes have been demonstrated. However, few studies have examined the effects of air pollution on liver enzyme levels. METHODS Blood samples were drawn up to three times between 2008 and 2010 from 545 elderly individuals who regularly visited a community welfare center in Seoul, Korea. Data regarding ambient air pollutants (particulate matter ≤2.5 μm [PM2.5], nitrogen dioxide [NO2], ozone [O3], carbon monoxide, and sulfur dioxide) from monitoring stations were used to estimate air pollution exposure. The effects of the air pollutants on the concentrations of three liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and γ-glutamyltranspeptidase [γ-GTP)]) were evaluated using generalized additive and linear mixed models. RESULTS Interquartile range increases in the concentrations of the pollutants showed significant associations of PM2.5 with AST (3.0% increase, p=0.0052), ALT (3.2% increase, p=0.0313), and γ-GTP (5.0% increase, p=0.0051) levels; NO2 with AST (3.5% increase, p=0.0060) and ALT (3.8% increase, p=0.0179) levels; and O3 with γ-GTP (5.3% increase, p=0.0324) levels. Significant modification of these effects by exercise and alcohol consumption was found (p for interaction <0.05). The effects of air pollutants were greater in non-exercisers and heavy drinkers. CONCLUSIONS Short-term exposure to air pollutants such as PM2.5, NO2, and O3 is associated with increased liver enzyme levels in the elderly. These adverse effects can be reduced by exercising regularly and abstinence from alcohol.
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Affiliation(s)
- Kyoung-Nam Kim
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hyemi Lee
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jin Hee Kim
- Department of Environmental Health, Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Kweon Jung
- Seoul Metropolitan Institute of Public Health and Environment, Seoul, Korea
| | - Youn-Hee Lim
- Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea ; Environmental Health Center, Seoul National University College of Medicine, Seoul, Korea
| | - Yun-Chul Hong
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea ; Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea ; Environmental Health Center, Seoul National University College of Medicine, Seoul, Korea
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Dey T, Gogoi K, Unni B, Bharadwaz M, Kalita M, Ozah D, Kalita M, Kalita J, Baruah PK, Bora T. Role of environmental pollutants in liver physiology: special references to peoples living in the oil drilling sites of Assam. PLoS One 2015; 10:e0123370. [PMID: 25874634 PMCID: PMC4395329 DOI: 10.1371/journal.pone.0123370] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2014] [Accepted: 02/25/2015] [Indexed: 11/18/2022] Open
Abstract
The populations residing near polluted sites are more prone to various types of diseases. The important causes of air pollution are the suspended particulate matter, respirable suspended particulate matter, sulfur dioxide and nitrogen dioxide. As limited information is available enumerating the effect of these pollutants on liver physiology of the population living near the polluted sites; in the present study, we tried to investigate their effect on liver of the population residing near the oil drilling sites since birth. In this study, a randomly selected 105 subjects (46 subjects from oil drilling site and 61 subjects from control site) aged above 30 years were taken under consideration. The particulate matter as well as the gaseous pollutants, sulfur dioxide and nitrogen dioxide, were analyzed through a respirable dust sampler. The level of alkaline phosphatase, alanine transaminase and aspartate transaminase enzymes in serum were measured by spectrophotometer. The generalized regression model studies suggests a higher concentration of respirable suspended particulate matter, suspended particulate matter and nitrogen dioxide lowers the alkaline phosphatase level (p<0.0001) by 3.5 times (95% CI 3.1-3.9), 1.5 times (95% CI 1.4 - 1.6) and 12 times (95% CI 10.74 -13.804), respectively in the exposed group. The higher concentration of respirable suspended particulate matter and nitrogen dioxide in air was associated with increase in alanine transaminase level (p<0.0001) by 0.8 times (95% CI 0.589-1.049) and by 2.8 times (95% CI 2.067-3.681) respectively in the exposed group. The increase in nitrogen dioxide level was also associated with increase in aspartate transaminase level (p<0.0001) by 2.5 times (95% CI 1.862 – 3.313) in the exposed group as compared to control group. Thus, the study reveals that long-term exposure to the environmental pollutants may lead to liver abnormality or injury of populations living in polluted sites.
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Affiliation(s)
- Tapan Dey
- Biotechnology Division, Council of Scientific & Industrial Research—North-East Institute of Science and Technology, Jorhat, Assam, India
| | - Kabita Gogoi
- Biotechnology Division, Council of Scientific & Industrial Research—North-East Institute of Science and Technology, Jorhat, Assam, India
| | - Balagopalan Unni
- Biotechnology Division, Council of Scientific & Industrial Research—North-East Institute of Science and Technology, Jorhat, Assam, India
- * E-mail:
| | - Moonmee Bharadwaz
- Biotechnology Division, Council of Scientific & Industrial Research—North-East Institute of Science and Technology, Jorhat, Assam, India
| | - Munmi Kalita
- Biotechnology Division, Council of Scientific & Industrial Research—North-East Institute of Science and Technology, Jorhat, Assam, India
| | - Dibyajyoti Ozah
- Biotechnology Division, Council of Scientific & Industrial Research—North-East Institute of Science and Technology, Jorhat, Assam, India
| | - Manoj Kalita
- Biotechnology Division, Council of Scientific & Industrial Research—North-East Institute of Science and Technology, Jorhat, Assam, India
| | - Jatin Kalita
- Biotechnology Division, Council of Scientific & Industrial Research—North-East Institute of Science and Technology, Jorhat, Assam, India
| | - Pranab Kumar Baruah
- Biotechnology Division, Council of Scientific & Industrial Research—North-East Institute of Science and Technology, Jorhat, Assam, India
| | - Thaneswar Bora
- Biotechnology Division, Council of Scientific & Industrial Research—North-East Institute of Science and Technology, Jorhat, Assam, India
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Chen LC, Lippmann M. Inhalation toxicology methods: the generation and characterization of exposure atmospheres and inhalational exposures. CURRENT PROTOCOLS IN TOXICOLOGY 2015; 63:24.4.1-24.4.23. [PMID: 25645246 PMCID: PMC4332412 DOI: 10.1002/0471140856.tx2404s63] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
In this unit, the need for laboratory-based inhalation toxicology studies, the historical background on adverse health effects of airborne toxicants, and the benefits of advance planning for the building of analytic options into the study design to maximize the scientific gains to be derived from the investments in the study are outlined. The following methods are described: (1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; (2) the delivery and distribution into and within whole-body exposure chambers, head-only exposure chambers, face-masks, and mouthpieces or nasal catheters; (3) options for on-line functional assays during and between exposures; and (4) options for serial non-invasive assays of response. In doing so, a description beyond exposures to single agents and simple mixtures is presented, and included are methods for evaluating biological responses to complex environmental mixtures. It is also emphasized that great care should be taken in the design and execution of such studies so that the scientific returns can be maximized both initially, and in follow-up utilization of archived samples of the exposure atmospheres, excreta, and tissues collected for histology.
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Affiliation(s)
- Lung-Chi Chen
- Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York
| | - Morton Lippmann
- Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York
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Trovato FM, Catalano D, Garozzo A, Martines GF, Pirri C, Trovato GM. ADV36 adipogenic adenovirus in human liver disease. World J Gastroenterol 2014; 20:14706-14716. [PMID: 25356033 PMCID: PMC4209536 DOI: 10.3748/wjg.v20.i40.14706] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 04/03/2014] [Accepted: 06/26/2014] [Indexed: 02/07/2023] Open
Abstract
Obesity and liver steatosis are usually described as related diseases. Obesity is regarded as exclusive consequence of an imbalance between food intake and physical exercise, modulated by endocrine and genetic factors. Non-alcoholic fatty liver disease (NAFLD), is a condition whose natural history is related to, but not completely explained by over-nutrition, obesity and insulin resistance. There is evidence that environmental infections, and notably adipogenic adenoviruses (ADV) infections in humans, are associated not only with obesity, which is sufficiently established, but also with allied conditions, such as fatty liver. In order to elucidate the role, if any, of previous ADV36 infection in humans, we investigated association of ADV36-ADV37 seropositivity with obesity and fatty liver in humans. Moreover, the possibility that lifestyle-nutritional intervention in patients with NAFLD and different ADV36 seropositive status, achieves different clinical outcomes on ultrasound bright liver imaging, insulin resistance and obesity was challenged. ADV36 seropositive patients have a more consistent decrease in insulin resistance, fatty liver severity and body weight in comparison with ADV36 seronegative patients, indicating a greater responsiveness to nutritional intervention. These effects were not dependent on a greater pre-interventional body weight and older age. These results imply that no obvious disadvantage - and, seemingly, that some benefit - is linked to ADV36 seropositivity, at least in NAFLD. ADV36 previous infection can boost weight loss and recovery of insulin sensitivity under interventional treatment.
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Kim JW, Park S, Lim CW, Lee K, Kim B. The role of air pollutants in initiating liver disease. Toxicol Res 2014; 30:65-70. [PMID: 25071914 PMCID: PMC4112066 DOI: 10.5487/tr.2014.30.2.065] [Citation(s) in RCA: 90] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Accepted: 06/28/2014] [Indexed: 12/16/2022] Open
Abstract
Recent episodes of severe air pollution in eastern Asia have been reported in the scientific literature and news media. Therefore, there is growing concern about the systemic effects of air pollution on human health. Along with the other well-known harmful effects of air pollution, recently, several animal models have provided strong evidence that air pollutants can induce liver toxicity and act to accelerate liver inflammation and steatosis. This review briefly describes examples where exposure to air pollutants was involved in liver toxicity, focusing on how particulate matter (PM) or carbon black (CB) may be translocated from lung to liver and what liver diseases are closely associated with these air pollutants.
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Affiliation(s)
- Jong Won Kim
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Jeonju, Korea
| | - Surim Park
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Jeonju, Korea
| | - Chae Woong Lim
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Jeonju, Korea
| | - Kyuhong Lee
- Inhalation Toxicology Research Center, Korea Institute of Toxicology, Jeonbuk, Korea ; Human and Environment Toxicology, University of Science and Technology, Daejeon, Korea
| | - Bumseok Kim
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Jeonju, Korea
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Regulatory T cells protect fine particulate matter-induced inflammatory responses in human umbilical vein endothelial cells. Mediators Inflamm 2014; 2014:869148. [PMID: 24987196 PMCID: PMC4060066 DOI: 10.1155/2014/869148] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Accepted: 05/06/2014] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE To investigate the role of CD4(+)CD25(+) T cells (Tregs) in protecting fine particulate matter (PM-) induced inflammatory responses, and its potential mechanisms. METHODS Human umbilical vein endothelial cells (HUVECs) were treated with graded concentrations (2, 5, 10, 20, and 40 µg/cm(2)) of suspension of fine particles for 24h. For coculture experiment, HUVECs were incubated alone, with CD4(+)CD25(-) T cells (Teff), or with Tregs in the presence of anti-CD3 monoclonal antibodies for 48 hours, and then were stimulated with or without suspension of fine particles for 24 hours. The expression of adhesion molecules and inflammatory cytokines was examined. RESULTS Adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and inflammatory cytokines, such as interleukin (IL-) 6 and IL-8, were increased in a concentration-dependent manner. Moreover, the adhesion of human acute monocytic leukemia cells (THP-1) to endothelial cells was increased and NF- κ B activity was upregulated in HUVECs after treatment with fine particles. However, after Tregs treatment, fine particles-induced inflammatory responses and NF- κ B activation were significantly alleviated. Transwell experiments showed that Treg-mediated suppression of HUVECs inflammatory responses impaired by fine particles required cell contact and soluble factors. CONCLUSIONS Tregs could attenuate fine particles-induced inflammatory responses and NF- κ B activation in HUVECs.
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Arciello M, Gori M, Maggio R, Barbaro B, Tarocchi M, Galli A, Balsano C. Environmental pollution: a tangible risk for NAFLD pathogenesis. Int J Mol Sci 2013; 14:22052-66. [PMID: 24213605 PMCID: PMC3856051 DOI: 10.3390/ijms141122052] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2013] [Revised: 10/18/2013] [Accepted: 10/24/2013] [Indexed: 12/13/2022] Open
Abstract
The liver is crucial for human life, and the health of this organ often mirrors the health of the individual. The liver can be the target of several diseases, the most prevalent of which, as a consequence of development and changes in human lifestyles, is the nonalcoholic fatty liver disease (NAFLD). NAFLD is a multifactorial disease that embraces many histo-pathologic conditions and is highly linked to metabolic derangements. Technological progress and industrialization have also had the consequence of releasing pollutants in the environment, for instance pesticides or solvents, as well as by-products of discharge, such as the particulate matter. In the last decade, a growing body of evidence has emerged, shedding light on the potential impact of environmental pollutants on liver health and, in particular, on NAFLD occurrence. These contaminants have a great steatogenic potential and need to be considered as tangible NAFLD risk factors. There is an urgent need for a deeper comprehension of their molecular mechanisms of action, as well as for new lines of intervention to reduce their worldwide diffusion. This review wishes to sensitize the community to the effects of several environmental pollutants on liver health.
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Affiliation(s)
- Mario Arciello
- Francesco Balsano Foundation, via G.B. Martini 6, Rome 00198, Italy; E-Mails: (M.A.); (M.G.); (R.M.); (B.B.)
| | - Manuele Gori
- Francesco Balsano Foundation, via G.B. Martini 6, Rome 00198, Italy; E-Mails: (M.A.); (M.G.); (R.M.); (B.B.)
- Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10, Ancona 60020, Italy
| | - Roberta Maggio
- Francesco Balsano Foundation, via G.B. Martini 6, Rome 00198, Italy; E-Mails: (M.A.); (M.G.); (R.M.); (B.B.)
| | - Barbara Barbaro
- Francesco Balsano Foundation, via G.B. Martini 6, Rome 00198, Italy; E-Mails: (M.A.); (M.G.); (R.M.); (B.B.)
| | - Mirko Tarocchi
- Gastroenterology Unit, Department of Experimental and Clinical Biochemical Sciences, University of Florence, Viale Pieraccini 6, Florence 50139, Italy; E-Mails: (M.T.); (A.G.)
| | - Andrea Galli
- Gastroenterology Unit, Department of Experimental and Clinical Biochemical Sciences, University of Florence, Viale Pieraccini 6, Florence 50139, Italy; E-Mails: (M.T.); (A.G.)
| | - Clara Balsano
- Francesco Balsano Foundation, via G.B. Martini 6, Rome 00198, Italy; E-Mails: (M.A.); (M.G.); (R.M.); (B.B.)
- Institute of Molecular Biology and Pathology (IBPM)-National Research Council (CNR), Piazzale Aldo Moro 7, Rome 00185, Italy
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +39-06-4993-3094; Fax: +39-06-4991-0908
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López-Navarrete G, Ramos-Martínez E, Suárez-Álvarez K, Aguirre-García J, Ledezma-Soto Y, León-Cabrera S, Gudiño-Zayas M, Guzmán C, Gutiérrez-Reyes G, Hernández-Ruíz J, Camacho-Arroyo I, Robles-Díaz G, Kershenobich D, Terrazas LI, Escobedo G. Th2-associated alternative Kupffer cell activation promotes liver fibrosis without inducing local inflammation. Int J Biol Sci 2011; 7:1273-86. [PMID: 22110380 PMCID: PMC3221364 DOI: 10.7150/ijbs.7.1273] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2011] [Accepted: 10/01/2011] [Indexed: 02/06/2023] Open
Abstract
Cirrhosis is the final outcome of liver fibrosis. Kupffer cell-mediated hepatic inflammation is considered to aggravate liver injury and fibrosis. Alternatively-activated macrophages are able to control chronic inflammatory events and trigger wound healing processes. Nevertheless, the role of alternative Kupffer cell activation in liver harm is largely unclear. Thus, we evaluated the participation of alternatively-activated Kupffer cells during liver inflammation and fibrosis in the murine model of carbon tetrachloride-induced hepatic damage. To stimulate alternative activation in Kupffer cells, 20 Taenia crassiceps (Tc) larvae were inoculated into BALBc/AnN female mice. Six weeks post-inoculation, carbon tetrachloride or olive oil were orally administered to Tc-inoculated and non-inoculated mice twice per week during other six weeks. The initial exposure of animals to T. crassiceps resulted in high serum concentrations of IL-4 accompanied by a significant increase in the hepatic mRNA levels of Ym-1, with no alteration in iNOS expression. In response to carbon tetrachloride, recruitment of inflammatory cell populations into the hepatic parenchyma was 5-fold higher in non-inoculated animals than Tc-inoculated mice. In contrast, carbon tetrachloride-induced liver fibrosis was significantly less in non-inoculated animals than in the Tc-inoculated group. The latter showed elevated IL-4 serum levels and low IFN-γ concentrations during the whole experiment, associated with hepatic expression of IL-4, TGF-β, desmin and α-sma, as well as increased mRNA levels of Arg-1, Ym-1, FIZZ-1 and MMR in Kupffer cells. These results suggest that alternative Kupffer cell activation is favored in a Th2 microenvironment, whereby such liver resident macrophages could exhibit a dichotomic role during chronic hepatic damage, being involved in attenuation of the inflammatory response but at the same time exacerbation of liver fibrosis.
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Affiliation(s)
- Qinghua Sun
- Division of Environmental Health Sciences, College of Public Health, Division of Cardiovascular Medicine, Ohio State University, Columbus, USA.
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