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Arnold CC, Maric I, Wong RJ, Tyson JE, Stevenson DK. Unbound bilirubin and risk of severe neurodevelopmental impairment in extremely low birthweight newborns. Pediatr Res 2025:10.1038/s41390-025-03872-x. [PMID: 39849115 DOI: 10.1038/s41390-025-03872-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 12/11/2024] [Accepted: 01/01/2025] [Indexed: 01/25/2025]
Abstract
BACKGROUND Unbound bilirubin (UB) was measured on day 5 ± 1 in 1101 ELBW newborns in the Aggressive vs Conservative Phototherapy randomized controlled trial. We accessed this dataset to quantify the UB-mediated risk of severe neurodevelopmental impairment (sNDI) in extremely low birthweight (ELBW) newborns. METHODS UB levels were standardized within laboratories as z-score percentiles. A dichotomous UB exposure variable was based on sharply increased risk of sNDI at the 85th percentile (UBz>85th). Targeted maximum likelihood estimation with ensemble machine learning (TMLE + ML) and logistic regression (LR) were used to estimate sNDI risk attributable to UBz>85th. RESULTS UB - total bilirubin correlation was poor: R2 0.24, 95% CI: 0.19, 0.30. The UB level corresponding to the UBz>85th cut-point in this cohort was estimated to be between 0.56 and 0.79 µg/dL. In 825 survivors with known sNDI status the crude risk difference (RD) associated with UBz>85th was 19.5%. With TMLE + ML, the RD was 14.4% (95% CI: 5.7%, 23.1%) corresponding to a number need to harm (NNH) of 7 (95% CI: 4, 18). LR results were similar: RD 12.4% (95% CI: 4.7%, 20.1%), NNH 8 (95% CI: 5, 21). CONCLUSIONS Exposure to UBz>85th was associated with a large increase in risk of sNDI in ELBW newborns. IMPACT Accessing the only large dataset with measures of unbound bilirubin (UB) and neurodevelopmental outcomes in extremely low birthweight (ELBW) newborns we found poor correlation between UB and total bilirubin (TB). The risk of severe neurodevelopmental impairment (sNDI) associated with UB rose non-linearly with an inflection point at UB z-score 85th percentile (UBz>85th), increasing the risk of sNDI by an estimated 14% (number need to harm: 7). The current incidence of exposure to harmful UB levels in very premature newborns is unlikely to be rare. TB levels provide a false sense of security to clinicians caring for very premature newborns.
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Affiliation(s)
- Cody C Arnold
- Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.
| | - Ivana Maric
- Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Ronald J Wong
- Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Jon E Tyson
- Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA
- Institute for Clinical Research and Learning Health Care, McGovern Medical School at UT Houston, Houston, TX, USA
| | - David K Stevenson
- Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA
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Zheng H, Zheng H, Wei L, Xue Z, Xu B, Hu M, Yu J, Xie R, Zhang L, Zheng Z, Xie J, Zheng C, Huang C, Lin J, Li P. Risk stratification models incorporating oxidative stress factors to predict survival and recurrence in patients with gastric cancer after radical gastrectomy: A real-world multicenter study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108658. [PMID: 39244978 DOI: 10.1016/j.ejso.2024.108658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 08/13/2024] [Accepted: 09/02/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND Oxidative stress significantly influences the development and progression of gastric cancer (GC). It remains unreported whether incorporating oxidative stress factors into nomograms can improve the predictive accuracy for survival and recurrence risk in GC patients. METHODS 3498 GC patients who underwent radical gastrectomy between 2009 and 2017 were enrolled and randomly divided into training cohort (TC) and internal validation cohort (IVC). Cox regression analysis model was used to evaluate six preoperative oxidative stress indicators to formulate the Systemic oxidative stress Score (SOSS). Two nomograms based on SOSS was constructed by multivariate Cox regression and validated using 322 patients from another two hospitals. RESULTS A total of 3820 patients were included. The SOSS, composed of three preoperative indicators-fibrinogen, albumin, and cholesterol-was an independent prognostic factor for both overall survival (OS) and disease-free survival (DFS). The two nomograms based on SOSS showed a significantly higher AUC than the pTNM stage (OS: 0.830 vs. 0.778, DFS: 0.824 vs. 0.775, all P < 0.001) and were validated in the IVC and EVC (all P < 0.001). The local recurrence rate, peritoneal recurrence rate, distant recurrence rate and multiple recurrence rate in high-risk group were significantly higher than those in low-risk group (P < 0.05). CONCLUSIONS The two novel nomograms based on SOSS which was a combination score of three preoperative blood indicators, demonstrated outstanding predictive abilities for both survival and recurrence in GC patients with different risk groups, which may potentially improve survival through perioperatively active intervention strategies and individualized postoperatively close surveillance.
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Affiliation(s)
- Honghong Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Hualong Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Linghua Wei
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Zhen Xue
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Binbin Xu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Minggao Hu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Department of General Surgery, The PLA Navy Anqing Hospital, Anqing, 246000, China
| | - Junhua Yu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Department of General Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China
| | - Rongzhen Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Department of General Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 321000, China
| | - Lingkang Zhang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Zhiwei Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Jianwei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Chaohui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - ChangMing Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China.
| | - Jianxian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China.
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China; Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China.
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Gulden S, Cervellini G, Colombo M, Marangoni MB, Taccani V, Pesenti N, Raffaeli G, Araimo G, Osnaghi S, Fumagalli M, Garrido F, Villamor E, Cavallaro G. Hyperbilirubinemia and retinopathy of prematurity: a retrospective cohort study. Eur J Pediatr 2024; 183:3809-3818. [PMID: 38877325 DOI: 10.1007/s00431-024-05630-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 05/22/2024] [Accepted: 05/24/2024] [Indexed: 06/16/2024]
Abstract
Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease in preterm infants. Oxidative stress plays a key role in the pathogenesis of ROP. Due to its antioxidant effects, bilirubin has been proposed to be protective against ROP. This study explored the association between hyperbilirubinemia and ROP. We analyzed a 10-year cohort from a neonatal intensive care unit in Milan, Italy, including 1606 infants born under 32 weeks and/or < 1500 g. Data from 1606 infants meeting specific inclusion criteria were reviewed. Eighty infants were excluded due to lack of data, 1526 were deemed eligible for analysis, and 1269 had hyperbilirubinemia requiring phototherapy. There was a higher incidence of ROP among infants with hyperbilirubinemia (13.8%) versus those without (7.8%, p<0.01). Infants with any ROP, non-severe or severe ROP, were exposed to hyperbilirubinemia for a significantly higher number of days compared with those without ROP. Each additional day of exposure increases the risk of developing any ROP by 5%, non-severe ROP by 4%, and severe ROP by 6%. However, this correlation was not observed in infants with gestational age less than 27 weeks and/or body weight less than 1000 g. Conclusion: Our data show that hyperbilirubinemia requiring phototherapy is associated with an increased risk of developing ROP. However, severe hyperbilirubinemia and ROP share many of their risk factors. Therefore, rather than being a risk factor itself, hyperbilirubinemia may be a surrogate for other risk factors for ROP. Clinical Trial Registration: NCT05806684. What is Known: • The development of retinopathy of prematurity (ROP) is influenced by several critical risk factors, including low gestational age, low birth weight, supplemental oxygen use, and increased oxidative stress. • In vitro, unconjugated bilirubin is an effective scavenger of harmful oxygen species and a reducing agent, highlighting its potential protective role against oxidative stress. What is New: • Hyperbilirubinemia requiring phototherapy was associated with an increased risk of developing ROP, but this association was not observed in the most vulnerable population of extremely preterm infants. • Every additional day of phototherapy for hyperbilirubinemia increases the risk of ROP by 5% for any ROP, 4% for non-severe ROP, and 6% for severe ROP.
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Affiliation(s)
- Silvia Gulden
- Neonatal Intensive Care Unit, Sant'Anna Hospital, 22042, Como, Italy
| | - Gaia Cervellini
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122, Milan, Italy
| | - Marta Colombo
- Neonatal Intensive Care Unit, Sant'Anna Hospital, 22042, Como, Italy
| | - Maria Beatrice Marangoni
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122, Milan, Italy
| | - Vittoria Taccani
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122, Milan, Italy
| | - Nicola Pesenti
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Revelo Datalabs S.R.L, 20142, Milan, Italy
| | - Genny Raffaeli
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy.
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122, Milan, Italy.
| | - Gabriella Araimo
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
| | - Silvia Osnaghi
- Department of Ophthalmology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122, Milan, Italy
| | - Monica Fumagalli
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122, Milan, Italy
| | - Felipe Garrido
- Neonatal Intensive Care Unit, Clínica Universidad de Navarra, 28027, Madrid, Spain
| | - Eduardo Villamor
- Division of Neonatology, MosaKids Children's Hospital, Maastricht University Medical Center (MUMC+), Research Institute for Oncology and Reproduction (GROW), Maastricht University, 6202AZ, Maastricht, The Netherlands
| | - Giacomo Cavallaro
- Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
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Wu G, Gu M, Zhu J, Gu R, Yang B, Ji S, Zhao Y, Gu K. Prognostic prediction of oxidative stress related hematological biomarkers in locally advanced cervical cancer patients undergoing chemoradiotherapy. Biomarkers 2024; 29:255-264. [PMID: 38767430 DOI: 10.1080/1354750x.2024.2358300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 05/11/2024] [Indexed: 05/22/2024]
Abstract
OBJECTIVE This investigation aimed to develop and validate a novel oxidative stress score for prognostic prediction in locally advanced cervical cancer (LACC) patients receiving chemoradiotherapy. METHODS A total of 301 LACC patients were enrolled and randomly divided into a training and a validation set. The association between oxidative stress parameters and prognosis was analyzed for oxidative stress score (OSS) establishment. A Cox regression model was conducted for overall survival (OS) and progression-free survival (PFS). A nomogram prediction model was developed using independent prognostic factors from the training set and validated in the validation set. RESULTS A novel OSS was established with four oxidative stress parameters, including albumin, total bilirubin, blood urea nitrogen, and lactate dehydrogenase. Multivariate regression analysis identified OSS as an independent prognostic factor for OS (p = 0.001) and PFS (p < 0.001). A predictive nomogram based on the OSS was established and validated. The C-indexes of the nomogram in the training set were 0.772 for OS and 0.781 for PFS, while in the validation set the C-indexes were 0.642 for OS and 0.621 for PFS. CONCLUSION This study confirmed that preoperative OSS could serve as a useful independent prognostic factor in LACC patients who received CCRT.
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Affiliation(s)
- Gang Wu
- Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, P.R. China
| | - Mengxuan Gu
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, P.R. China
| | - Jiahao Zhu
- Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, P.R. China
| | - Ruike Gu
- Department of Rehabilitation Medical, Suzhou Rehabilitation Hospital (Suzhou Municipal Hospital Rehabilitation Medical Center), Suzhou, Jiangsu, P.R. China
| | - Bo Yang
- Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, P.R. China
| | - Shengjun Ji
- Department of Radiotherapy and Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, P.R. China
| | - Yutian Zhao
- Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, P.R. China
| | - Ke Gu
- Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, P.R. China
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Endesfelder S, Schmitz T, Bührer C. Bilirubin Exerts Protective Effects on Alveolar Type II Pneumocytes in an In Vitro Model of Oxidative Stress. Int J Mol Sci 2024; 25:5323. [PMID: 38791361 PMCID: PMC11121655 DOI: 10.3390/ijms25105323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 05/07/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
Newborn infants face a rapid surge of oxygen and a more protracted rise of unconjugated bilirubin after birth. Bilirubin has a strong antioxidant capacity by scavenging free radicals, but it also exerts direct toxicity. This study investigates whether cultured rat alveolar epithelial cells type II (AEC II) react differently to bilirubin under different oxygen concentrations. The toxic threshold concentration of bilirubin was narrowed down by means of a cell viability test. Subsequent analyses of bilirubin effects under 5% oxygen and 80% oxygen compared to 21% oxygen, as well as pretreatment with bilirubin after 4 h and 24 h of incubation, were performed to determine the induction of apoptosis and the gene expression of associated transcripts of cell death, proliferation, and redox-sensitive transcription factors. Oxidative stress led to an increased rate of cell death and induced transcripts of redox-sensitive signaling pathways. At a non-cytotoxic concentration of 400 nm, bilirubin attenuated oxidative stress-induced responses and possibly mediated cellular antioxidant defense by influencing Nrf2/Hif1α- and NFκB-mediated signaling pathways. In conclusion, the study demonstrates that rat AEC II cells are protected from oxidative stress-induced impairment by low-dose bilirubin.
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Affiliation(s)
- Stefanie Endesfelder
- Department of Neonatology, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (T.S.); (C.B.)
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Ahmed MZH, Saad RHAH, Gadalla A, Thabet RHI, Elsisi AAE, Ahmed Mohamed AAN, Abdallah MG, Shikhon T, Hussien Mohmmed Maged HE, Hassan Elfiky MA, Hassan MF, Abdelraheem FM, Hegazy GA. The association of oxidative stress of neonatal hyperbilirubinemia and vitamin E supplementation. Clin Exp Hepatol 2024; 10:30-38. [PMID: 38765909 PMCID: PMC11100342 DOI: 10.5114/ceh.2024.136230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 10/26/2023] [Indexed: 05/22/2024] Open
Abstract
Aim of the study Jaundice in newborns is a sign of skin and sclera pigmentation. Hyperbilirubinemia and these phenomena do, however, have a relationship. According to many clinical studies, elevated blood bilirubin and low vitamin E (VE) levels in newborns are associated. The aim of the study was to investigate the association of oxidative stress of neonatal hyperbilirubinemia in patients who underwent phototherapy with additional vitamin E supplementation (25 mg/kg/day over the course of three days) and patients without additional vitamin E. Material and methods A set of 100 neonatal indirect hyperbilirubinemia patients was enrolled at neonatal intensive care units (NICUs) of the pediatric departments at Al Azhar University Hospitals during the period from February 2021 to October 2022 after obtaining signed written informed consent of all neonates' parents with an explanation of the aim of study. Results Significant differences were found between the studied groups regarding serum bilirubin on the third day of admission (p = 0.039). Patients who were treated with vitamin E had lower serum bilirubin on the third day of admission (8.25 ±3.41) than the control group (11.66 ±3.22). Also, among the VE group, serum bilirubin was significantly decreased on the third day of admission (8.25 ±3.41) compared to zero days of admission (14.10 ±4.39) (p = 0.041). Conclusions Vitamin E supplementation has an important role in treatment of indirect hyperbilirubinemia in neonates. Early administration of vitamin E in preterm neonates resulted in a significant decrease of serum bilirubin and increased total antioxidant capacity. Vitamin E supplementation in full term decreased the duration of phototherapy.
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Affiliation(s)
| | | | - Ahmad Gadalla
- Physiology Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | | | | | | | | | - Tarek Shikhon
- Biochemistry Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | | | | | - Marwa Fekry Hassan
- Community and Public Health Department, National Liver Institute, Menoufia University, Shebin elkom, Menoufia, Egypt
| | | | - Ghada Adel Hegazy
- Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Shebin elkom, Menoufia, Egypt
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Kakinuma K, Kakinuma T. Analysis of oxidative stress and antioxidative potential in premature ovarian insufficiency. World J Clin Cases 2023; 11:2684-2693. [PMID: 37214574 PMCID: PMC10198121 DOI: 10.12998/wjcc.v11.i12.2684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/20/2023] [Accepted: 03/23/2023] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND Premature ovarian insufficiency (POI) is characterized by an early decline in ovarian function, inducing secondary amenorrhea. While the cause of POI has not yet been identified, the function of mitochondria in the ovaries and the cytotoxicity associated with reactive oxygen species (ROS) have been implicated in follicle pool depletion and a decline in follicle quality. Recently developed tests have enabled easy measurement of diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). The combination of these two tests is used to comprehensively assess oxidative stress in the blood.
AIM To comprehensively assess the oxidative stress of d-ROMs and BAP in POI.
METHODS Participants were classified into two groups: A POI group of 11 women aged < 40 years examined between January 2021 and June 2022 with a history of secondary amenorrhea for at least 4 mo in our hospital and an FSH value of ≥ 40 mIU/mL; and a control group of healthy women of the same age with normal ovarian function in our hospital. Plasma d-ROMs and BAP were measured in both these groups underwent. Differences between groups were assessed using the t-test.
RESULTS The mean age and mean body mass index (BMI) were 35.8 ± 3.0 years and 20.1 ± 1.9 kg/m2 in the control group and 35.8 ± 2.7 years and 19.4 ± 2.5 kg/m2 in the POI group, respectively. The mean gravidity and parity in control and POI groups were 0.6 ± 0.7 and 0.4 ± 0.5 and 0.6 ± 0.9 and 0.3 ± 0.5, respectively. The two groups did not differ significantly in terms of mean age, BMI, gravidity, or parity. The d-ROMs level was significantly higher in the POI group than in the control group (478.2 ± 58.7 vs 341.1 ± 35.1 U.CARR; P < 0.001); however, the BAP level did not significantly differ between the two groups (2078.5 ± 157.4 vs 2029.0 ± 186.4 μmol/L). The oxidase stress index (d-ROMs/BAP × 100) was significantly higher in the POI group than in the control group (23.7 ± 3.3 vs 16.5 ± 2.1; P < 0.001).
CONCLUSION Oxidative stress was significantly greater in the POI group than in the control group, suggesting oxidative stress as a factor that can serve as a POI biomarker.
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Affiliation(s)
- Kaoru Kakinuma
- Department of Obstetrics and Gynecology, International Health and Welfare Hospital, Nasushiobara 327-2763, Japan
| | - Toshiyuki Kakinuma
- Department of Obstetrics and Gynecology, International Health and Welfare Hospital, Nasushiobara 327-2763, Japan
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Nocentini A, Bonardi A, Pratesi S, Gratteri P, Dani C, Supuran CT. Pharmaceutical strategies for preventing toxicity and promoting antioxidant and anti-inflammatory actions of bilirubin. J Enzyme Inhib Med Chem 2022; 37:487-501. [PMID: 34986721 PMCID: PMC8741241 DOI: 10.1080/14756366.2021.2020773] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 12/02/2021] [Accepted: 12/03/2021] [Indexed: 12/25/2022] Open
Abstract
Bilirubin (BR) is the final product of haem catabolism. Disruptions along BR metabolic/transport pathways resulting from inherited disorders can increase plasma BR concentration (hyperbilirubinaemia). Unconjugated hyperbilirubinemia may induce BR accumulation in brain, potentially causing irreversible neurological damage, a condition known as BR encephalopathy or kernicterus, to which newborns are especially vulnerable. Numerous pharmaceutical strategies, mostly based on hemoperfusion, have been proposed over the last decades to identify new valid, low-risk alternatives for BR removal from plasma. On the other hand, accumulating evidence indicates that BR produces health benefits due to its potent antioxidant, anti-inflammatory and immunomodulatory action with a significant potential for the treatment of a multitude of diseases. The present manuscript reviews both such aspects of BR pharmacology, gathering literature data on applied pharmaceutical strategies adopted to: (i) reduce the plasma BR concentration for preventing neurotoxicity; (ii) produce a therapeutic effect based on BR efficacy in the treatment of many disorders.
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Affiliation(s)
- Alessio Nocentini
- Department of Neurosciences, Psychology, Drug Research and Child Health, Pharmaceutical and Nutraceutical Section, University of Florence, Florence, Italy
| | - Alessandro Bonardi
- Department of Neurosciences, Psychology, Drug Research and Child Health, Pharmaceutical and Nutraceutical Section, University of Florence, Florence, Italy
| | - Simone Pratesi
- Department of Neurosciences, Psychology, Drug Research and Child Health, Careggi University, Hospital of Florence, Florence, Italy
| | - Paola Gratteri
- Department of Neurosciences, Psychology, Drug Research and Child Health, Pharmaceutical and Nutraceutical Section, Laboratory of Molecular Modelling Cheminformatics & QSAR, University of Florence, Florence, Italy
| | - Carlo Dani
- Department of Neurosciences, Psychology, Drug Research and Child Health, Careggi University, Hospital of Florence, Florence, Italy
| | - Claudiu T. Supuran
- Department of Neurosciences, Psychology, Drug Research and Child Health, Pharmaceutical and Nutraceutical Section, University of Florence, Florence, Italy
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Raba AA, O'Sullivan A, Miletin J. The Possible Protective Role of Bilirubin on Oxidative Stress Related Morbidity in Preterm Infants. Fetal Pediatr Pathol 2022; 41:904-908. [PMID: 34821525 DOI: 10.1080/15513815.2021.2008069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
To evaluate the effect of bilirubin levels in the first week of life on the frequency of oxidative-stress related morbidity. We included all preterm infants with a gestational age less than 32 weeks. The mean total serum bilirubin of the first week of life was measured and compared between infants with and without oxidative stress related morbidity. A total of 116 preterm infants were included. Univariate analysis showed that mean ± SD TSB levels were statistically significantly lower in infants with chronic lung disease (95 ± 31.4micromole/l vs 119 ± 31micromole/l, p = 0.019), necrotizing enterocolitis (94.4 ± 29micromole/l vs 118 ± 31micromole/l p = 0.044) and patent ductus arteriosus (104 ± 33micromole/l vs 120 ± 30micromole/l p = 0.018). However, when adjusted for gestational age, there were no longer statistically significant differences observed. Elevated bilirubin levels in the first week of life are not protective against the oxidative stress related morbidity in very preterm infants.
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Affiliation(s)
- Ali Ahmed Raba
- Department of Paediatrics and Newborn Medicine, Coombe Women and Infants University Hospital, Dublin, Ireland.,UCD School of Medicine and Medical Sciences, Dublin, Ireland
| | - Anne O'Sullivan
- Department of Paediatrics and Newborn Medicine, Coombe Women and Infants University Hospital, Dublin, Ireland
| | - Jan Miletin
- Department of Paediatrics and Newborn Medicine, Coombe Women and Infants University Hospital, Dublin, Ireland.,UCD School of Medicine and Medical Sciences, Dublin, Ireland.,Institute for the Care of Mother and Child, Prague, Czech Republic.,3rd School of Medicine, Charles University, Prague, Czech Republic
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10
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Pranty AI, Shumka S, Adjaye J. Bilirubin-Induced Neurological Damage: Current and Emerging iPSC-Derived Brain Organoid Models. Cells 2022; 11:2647. [PMID: 36078055 PMCID: PMC9454749 DOI: 10.3390/cells11172647] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 08/04/2022] [Accepted: 08/17/2022] [Indexed: 11/16/2022] Open
Abstract
Bilirubin-induced neurological damage (BIND) has been a subject of studies for decades, yet the molecular mechanisms at the core of this damage remain largely unknown. Throughout the years, many in vivo chronic bilirubin encephalopathy models, such as the Gunn rat and transgenic mice, have further elucidated the molecular basis of bilirubin neurotoxicity as well as the correlations between high levels of unconjugated bilirubin (UCB) and brain damage. Regardless of being invaluable, these models cannot accurately recapitulate the human brain and liver system; therefore, establishing a physiologically recapitulating in vitro model has become a prerequisite to unveil the breadth of complexities that accompany the detrimental effects of UCB on the liver and developing human brain. Stem-cell-derived 3D brain organoid models offer a promising platform as they bear more resemblance to the human brain system compared to existing models. This review provides an explicit picture of the current state of the art, advancements, and challenges faced by the various models as well as the possibilities of using stem-cell-derived 3D organoids as an efficient tool to be included in research, drug screening, and therapeutic strategies for future clinical applications.
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Affiliation(s)
| | | | - James Adjaye
- Institute for Stem Cell Research and Regenerative Medicine, Faculty of Medicine, Heinrich-Heine University, Moorenstrasse 5, 40225 Dusseldorf, Germany
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11
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Vázquez-Lorente H, Herrera-Quintana L, Molina-López J, Gamarra-Morales Y, López-González B, Planells E. Relationship between Body Composition and Biochemical Parameters with Antioxidant Status in a Healthy Cohort of Postmenopausal Women. Metabolites 2022; 12:metabo12080746. [PMID: 36005618 PMCID: PMC9412505 DOI: 10.3390/metabo12080746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/11/2022] [Accepted: 08/12/2022] [Indexed: 11/24/2022] Open
Abstract
An adequate prooxidant–antioxidant balance—which may be influenced by body composition and biochemical status—is essential to maintain human health, especially in circumstances under which the antioxidant defense decreases, such as menopause. The present study aimed to examine the relationship between body composition and biochemical parameters with antioxidant status in a healthy cohort of postmenopausal women. This cross-sectional study was carried out in a cohort of 78 postmenopausal women aged 44–76 years. The body composition profile was assessed through bioelectrical impedance. The determination of the total antioxidant capacity and superoxide dismutase activity was conducted by the colorimetric method, and glutathione peroxidase activity was determined by the enzymatic immunological method. The vitamin D levels were measured by ultra-performance liquid chromatography–tandem mass spectrometry. The mineral status was assessed through flame atomic absorption spectrophotometry. The rest of the biochemical parameters were assessed through an immunoassay. The total antioxidant capacity and antioxidant gap were negatively influenced by body composition (all p ≤ 0.049) and positively related to protein metabolism parameters (all p ≤ 0.048), whereas circulating levels of different micronutrients (all p ≤ 0.048) and enzymes (all p ≤ 0.047) appeared to play an important role in the glutathione peroxidase and superoxide dismutase activities. In conclusion, the menopause-related antioxidant status changes may be influenced by key body composition and biochemical profiles. To confirm this statement, further trials aiming to evaluate the body composition and biochemical intervention-induced changes upon antioxidant defense are needed.
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Affiliation(s)
- Héctor Vázquez-Lorente
- Institute of Nutrition and Food Technology “José Mataix”, University of Granada, 18071 Granada, Spain
| | - Lourdes Herrera-Quintana
- Institute of Nutrition and Food Technology “José Mataix”, University of Granada, 18071 Granada, Spain
- Correspondence: (L.H.-Q.); (J.M.-L.)
| | - Jorge Molina-López
- Faculty of Education, Psychology and Sports Sciences, University of Huelva, Avd. De las Fuerzas Armadas S/N, 21007 Huelva, Spain
- Correspondence: (L.H.-Q.); (J.M.-L.)
| | - Yenifer Gamarra-Morales
- Institute of Nutrition and Food Technology “José Mataix”, University of Granada, 18071 Granada, Spain
| | - Beatriz López-González
- Institute of Nutrition and Food Technology “José Mataix”, University of Granada, 18071 Granada, Spain
| | - Elena Planells
- Institute of Nutrition and Food Technology “José Mataix”, University of Granada, 18071 Granada, Spain
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12
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Zhang X, Barr DB, Dunlop AL, Panuwet P, Sarnat JA, Lee GE, Tan Y, Corwin EJ, Jones DP, Ryan PB, Liang D. Assessment of metabolic perturbations associated with exposure to phthalates among pregnant African American women. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 818:151689. [PMID: 34793805 PMCID: PMC8904271 DOI: 10.1016/j.scitotenv.2021.151689] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 11/07/2021] [Accepted: 11/10/2021] [Indexed: 05/17/2023]
Abstract
BACKGROUND Phthalates have been linked with numerous harmful health effects. Limited data are available on the molecular mechanism underlying phthalate toxicity on human health. In this study, we measured urinary phthalate metabolites and used high-resolution metabolomics (HRM) to identify biological perturbations associated with phthalate exposures among pregnant African American (AA) women, who are disproportionately exposed to high phthalates levels. METHODS We used untargeted HRM profiling to characterize serum samples collected during early (8-14 weeks gestation) and late (24-30 weeks gestation) pregnancy from 73 participants from the Atlanta AA Maternal-Child cohort. We measured eight urinary phthalate metabolites in early and late pregnancy, including Monoethyl phthalate (MEP), Mono(2-ethlyhexyl) phthalate (MEHP), and Mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), to assess maternal exposures to phthalates. Metabolite and metabolic pathway perturbation were evaluated using an untargeted HRM workflow. RESULTS Geometric mean creatinine-adjusted levels of urinary MEP, MEHP, and MEHHP were 67.3, 1.4, and 4.1 μg/g creatinine, respectively, with MEP and MEHP higher than the mean levels of non-Hispanic blacks in the general US population (2015-2016). There were 73 and 1435 metabolic features significantly associated with at least one phthalate metabolite during early and late pregnancy (p < 0.005), respectively. Pathway enrichment analysis revealed perturbations in four inflammation- and oxidative-stress-related pathways associated with phthalate metabolite levels during both early and late pregnancy, including glycerophospholipid, urea cycle, arginine, and tyrosine metabolism. We confirmed 10 metabolites with level-1 evidence, which are associated with urinary phthalates, including thyroxine and thiamine, which were negatively associated with MEP, as well as tyramine and phenethylamine, which were positively associated with MEHP and MEHHP. CONCLUSION Our results demonstrated that urinary phthalate levels were associated with perturbations in biological pathways connected with inflammation, oxidative stress, and endocrine disruption. The findings support future targeted investigations on molecular mechanisms underlying the impact of maternal phthalates exposure on adverse health outcomes.
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Affiliation(s)
- Xiaoyue Zhang
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Dana Boyd Barr
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Anne L Dunlop
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA
| | - Parinya Panuwet
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Jeremy A Sarnat
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Grace E Lee
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Youran Tan
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | | | - Dean P Jones
- Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA
| | - P Barry Ryan
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Donghai Liang
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
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13
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Midan DAR, Bahbah WA, Bayomy NR, Ashour NM. Clinical Assessment of Neuroinflammatory Markers and Antioxidants in Neonates with Hyperbilirubinemia and Their Association with Acute Bilirubin Encephalopathy. CHILDREN (BASEL, SWITZERLAND) 2022; 9:559. [PMID: 35455603 PMCID: PMC9027937 DOI: 10.3390/children9040559] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 03/07/2022] [Accepted: 04/11/2022] [Indexed: 12/28/2022]
Abstract
Objective: To assess the oxidant and antioxidant status in neonates with and without hyperbilirubinemia and their association with early manifestations of acute bilirubin encephalopathy (ABE), in addition to eliciting the possible oxidative effects of phototherapy. Methods: This prospective observational study was conducted with 104 full-term newborns at Menoufia University Hospitals from January 2020 to January 2021 to help resolve the debate regarding whether bilirubin is an antioxidant. The cases group (Group I) included 52 full-term newborns (37−40 weeks) with hyperbilirubinemia during the neonatal period, while the control group (Group II) included 52 healthy, full-term age and sex-matched newborns who did not have hyperbilirubinemia. The cases group was further subdivided into Group Ia (n = 12), which included newborns who presented with neurological manifestations suggesting early ABE, and Group Ib (n = 40), which included newborns with no signs suggestive of ABE. All newborns were subjected to clinical and neurological examinations, as well as laboratory investigations. Results: Comparing the specific biological markers between the Group 1 subgroups before phototherapy, the mean plasma levels of prostaglandin-Em, prostaglandin E2, and TSB were significantly higher in Subgroup I(a) (all p < 0.05). After phototherapy, Subgroup I(a) patients had significantly higher levels of prostaglandin-Em, DSB, and TSB (p < 0.05). The biological marker levels improved after phototherapy in terms of TAC (0.811 vs. 0.903), MDA (8.18 vs. 5.13), prostaglandin-Em (37.47 vs. 27.23), prostaglandin E2 (81.09 vs. 31.49), DSB (1.21 vs. 0.55), and TSB (16.63 vs. 8.26; p-value < 0.05). Conclusion: Our study showed that an elevated level of serum bilirubin increases oxidative stress and decreases antioxidant capacity. The reduction in bilirubin levels by phototherapy is associated with a decrease in oxidative stress markers (MDA, PGEm, and PGE2) and an upsurge in TAC, highlighting the absence of oxidative stress effects arising from phototherapy. Neonates with neurological manifestations suggesting ABE had higher levels of oxidative stress markers and lower levels of total antioxidant capacity than those without.
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Affiliation(s)
- Dina Abdel Razek Midan
- Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia 32511, Egypt; (W.A.B.); (N.M.A.)
| | - Wael A. Bahbah
- Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia 32511, Egypt; (W.A.B.); (N.M.A.)
| | - Noha Rabie Bayomy
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Menoufia 32511, Egypt;
| | - Noha M. Ashour
- Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia 32511, Egypt; (W.A.B.); (N.M.A.)
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14
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Yu Y, Choi J, Lee MH, Kim K, Ryu HM, Han HW. Maternal disease factors associated with neonatal jaundice: a case-control study. BMC Pregnancy Childbirth 2022; 22:247. [PMID: 35331174 PMCID: PMC8953140 DOI: 10.1186/s12884-022-04566-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 02/28/2022] [Indexed: 12/27/2022] Open
Abstract
Background Neonatal jaundice is common, and despite the considerable medical costs associated with it, there are still few studies on the maternal factors associated with it. Identification of maternal factors associated with neonatal jaundice is very important in terms of prevention, screening and management of neonatal jaundice. The current study aimed to identify maternal disease factors associated with neonatal jaundice. Methods We compared the maternal disease diagnostic codes during pregnancy (study A) and 1 year before conception (study B) in mothers whose insurance claims data included newborns treated for neonatal jaundice before birth registration via the National Health Insurance Service–National Sample Cohort (control group). To decrease the effect of confounding variables, the neonatal jaundice and control groups were matched at a ratio of 1:10 via propensity score matching using covariates including age and income. Results The matched samples for studies A and B included 4,026 and 3,278 (jaundice group: 366 and 298) delivery cases, respectively. In both studies, the jaundice group had a higher proportion of patients who underwent cesarean section than the control group. In study A, other diseases of the digestive system had the highest odds ratio (OR) (K92; adjusted OR: 14.12, 95% confidence interval [CI]: 2.70–82.26). Meanwhile, gastritis and duodenitis had the lowest OR (K29; adjusted OR: 0.39, 95% CI: 0.22–0.69). In study B, salpingitis and oophoritis had the highest OR (N70; adjusted OR: 3.33, 95% CI: 1.59–6.94). Heartburn had the lowest OR (R12; adjusted OR: 0.29, 95% CI:0.12–0.71). Conclusions This study identified maternal disease factors correlated with neonatal jaundice during pregnancy and 1 year before conception. Maternal risk factors for neonatal jaundice included syphilis and leiomyoma during pregnancy, and salpingo-oophoritis before pregnancy. The protective factors included infection, inflammatory diseases, and dyspepsia.
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Affiliation(s)
- Youngjae Yu
- Department of Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, Korea.,Institute for Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, Republic of Korea
| | - Jinwha Choi
- Department of Pediatrics, Korea University College of Medicine, Seoul, Korea
| | - Myeong Hoon Lee
- Department of Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, Korea.,Institute for Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, Republic of Korea
| | - KangHyun Kim
- Department of Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, Korea.,Institute for Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, Republic of Korea
| | - Hyun Mee Ryu
- Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Hyun Wook Han
- Department of Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, Korea. .,Institute for Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, Republic of Korea.
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15
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Lu Z, Wen T, Wang Y, Kan W, Xun G. Peripheral non-enzymatic antioxidants in patients with schizophrenia: a case-control study. BMC Psychiatry 2020; 20:241. [PMID: 32414343 PMCID: PMC7227358 DOI: 10.1186/s12888-020-02635-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Accepted: 04/29/2020] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND Recent studies show that oxidative stress is associated with the pathogenesis of schizophrenia. There are two major types of antioxidant systems in vivo, namely enzymatic antioxidants and non-enzymatic antioxidants. This study investigated differences of non-enzymatic antioxidants between schizophrenia patients and healthy controls. METHODS Peripheral UA, ALB, and TBIL of 107 schizophrenic patients in the acute stage and 101 in the remission stage were measured respectively, so were 273 healthy controls. RESULTS The levels of UA (P = 0.020) and TBIL (P < 0.001) of schizophrenic patients in the acute stage were higher than those of healthy controls, while the level of ALB (P < 0.001) was lower. Similar results were detected form schizophrenic patients in the remission stage. Schizophrenic patients in the acute stage were divided into antipsychotics-use subgroup (n = 56) and antipsychotics-naïve/free subgroup (n = 51). The level of UA (P = 0.001) in the antipsychotics-use subgroup was higher than that in the antipsychotics-naïve/free subgroup, while the level of TBIL (P = 0.002) was lower than that in the antipsychotics-naïve/free subgroup. Seventy-seven schizophrenic patients in the acute stage were followed up, and there was no significant difference in the level of UA before and after treatment, but levels of ALB (P < 0.001) and TBIL (P < 0.001) decreased significantly after the treatment. CONCLUSION This study demonstrated that the dysfunction of the peripheral non-enzymatic anti-oxidation system might be involved in the pathogenesis of schizophrenia.
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Affiliation(s)
- Zhe Lu
- Cheeloo College of Medicine, Shandong University, 44# Wenhua Western Road, Jinan, 250012, China
| | - Tianyang Wen
- Shandong Mental Health Center, 49# Wenhua Eastern Road, Jinan, 250014, China
| | - Yingtan Wang
- Department of Mental Health, Jining Medical University, 133# Hehua Road, Beihu New District, Jining, 272067, China
| | - Weijing Kan
- Beijing An Ding Hospital, Capital Medical University, China National Clinical Research Center for Mental Disorders, Beijing, People's Republic of China
| | - Guanglei Xun
- Shandong Mental Health Center, 49# Wenhua Eastern Road, Jinan, 250014, China.
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16
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Matsuura T, Kaneko H, Takayama K, Shibata R, Kataoka K, Ito S, Tsunekawa T, Shimizu H, Suzumura A, Namba R, Ito Y, Murohara T, Terasaki H. Diacron reactive oxygen metabolites and biological antioxidant potential tests for patients with age-related macular degeneration. BMC Ophthalmol 2020; 20:56. [PMID: 32070305 PMCID: PMC7027115 DOI: 10.1186/s12886-020-01334-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 02/06/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Previously, we showed that serum malondialdehyde (MDA) was significantly higher in patients with neovascular age-related macular degeneration (nAMD) than in those without AMD. The Diacron reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) tests are known markers of oxidative stress. The aim of this study was to use d-ROMs and BAP tests to evaluate changes in systemic oxidative stress in patients with nAMD. METHODS Blood serum samples were collected from 34 patients with nAMD (mean age: 76.5 ± 7.7 years; 22 men) and 20 control subjects (mean age: 62.9 ± 14.0 years; 10 men), and d-ROMs and BAP tests were examined. RESULTS In men, the mean level of d-ROMs for the nAMD patients was significantly higher than that for the controls (312.0 ± 52.4 vs. 275.1 ± 45.5 U.CARR, respectively; P < .05). There was a significant correlation between d-ROM level and CNV lesion area in the male nAMD group (r = .42, P = .05). There were no significant differences in mean BAP test results between the nAMD patients and controls for either sex (men: 2241 ± 549 vs. 2136 ± 246 μmol/L; women: 2263 ± 292 vs. 2335 ± 161 μmol/L). CONCLUSION The d-ROMs test may provide a useful indicator of nAMD in men but not in women.
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Affiliation(s)
- Toshiyuki Matsuura
- Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Hiroki Kaneko
- Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - Kei Takayama
- Department of Ophthalmology, National Defense Medical College, Saitama, Japan
| | - Rei Shibata
- Department of Advanced Cardiovascular Therapeutics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Keiko Kataoka
- Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Seina Ito
- Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Taichi Tsunekawa
- Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Hideyuki Shimizu
- Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Ayana Suzumura
- Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Rina Namba
- Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Yasuki Ito
- Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Toyoaki Murohara
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroko Terasaki
- Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
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17
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Kumar J, Yadav J. Neonatal hyperbilirubinaemia and type I diabetes: an unsolved enigma. Paediatr Int Child Health 2020; 40:72-73. [PMID: 31960786 DOI: 10.1080/20469047.2019.1660030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- Jogender Kumar
- Division of Neonatology, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India,
| | - Jaivinder Yadav
- Division of Endocrinology, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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18
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Bulut O, Erek A, Duruyen S. Effects of hyperbilirubinemia on markers of genotoxicity and total oxidant and antioxidant status in newborns. Drug Chem Toxicol 2020; 45:451-455. [DOI: 10.1080/01480545.2019.1710182] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Ozgul Bulut
- Department of Pediatrics, Division of Neonatology, Istanbul Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey
| | - Aybala Erek
- Department of Biochemistry, Istanbul Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey
| | - Sadettin Duruyen
- Department of Biochemistry, Istanbul Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey
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19
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Abstract
Hyperbilirubinemia is the most frequent clinical problem neonatologists must deal with during the newborn period. It has been suggested that bilirubin is involved in the balance between antioxidant and pro-oxidant agents due to its antioxidant properties. However, the relevance of these effects in vivo in term and preterm infants is still debated. We performed a literature review of studies that investigated the association between total serum bilirubin (TSB) and oxidative stress in newborn infants. We found that studies in term infants give contradictory results, while studies in preterm infants suggest that the TSB increase is associated with an oxidative stress increase due to concurrent factors other than bilirubin level, such as heme oxygenase (HO) activity. Moreover, it could be speculated that low physiologic TSB values are associated with antioxidant effects, while high pathologic TSB values are associated with pro-oxidant effects. Literature data do not allow the establishment of whether if the antioxidant properties of bilirubin are important from a clinical point of view and can affect the outcome in ill infants.
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Affiliation(s)
- Carlo Dani
- a Division of Neonatology , Careggi University Hospital of Florence , Florence , Italy.,b Department of Neurosciences, Psychology , Drug Research and Child Health, Careggi University Hospital of Florence , Florence , Italy
| | - Chiara Poggi
- a Division of Neonatology , Careggi University Hospital of Florence , Florence , Italy
| | - Simone Pratesi
- a Division of Neonatology , Careggi University Hospital of Florence , Florence , Italy
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20
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Kobayashi H, Iorio EL, Yoshino A. Effects of mode of delivery on pro-oxidant/antioxidant balance in fetal circulation. J Matern Fetal Neonatal Med 2018; 32:3294-3299. [PMID: 30231659 DOI: 10.1080/14767058.2018.1526911] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
Objective: This study was undertaken to assess the influence of mode of delivery on the balance between pro-oxidant/antioxidant systems in fetal circulation. Materials and methods: Both umbilical arterial and venous blood samples were obtained from 37 pregnant women who delivered by spontaneous vaginal delivery (VD group) and from 29 pregnant women who delivered by elective cesarean section (CS group). Oxidative stress and antioxidant activity were evaluated by reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP), respectively. Results: The d-ROMs values of the VD group were higher than that of the CS group in both umbilical arterial and venous blood and these differences were found to be statistically significant (p < .01 and p < .01, respectively). The BAP values of only the umbilical arterial blood were found to be statistically significant (p < .01), with values from the VD group being higher than those of the CS group. In all measurements, the d-ROMs values averaged below 120 CARR U and BAP values averaged above 2200 µmol/L. The ratio of BAP/d-ROMs difference was found to be statistically significant (p < .01) only in the umbilical venous blood, with ratios in the VD group being lower than those in the CS group. Conclusions: Our statistical analyses suggest that vaginal delivery has an effect on increasing oxidative stress as a result of the stress of labor and that an elective cesarean section does not impair the mother's oxidative stress status. Furthermore, the high BAP values in all the measurements suggest that neonates just after birth have the ability to cope with oxidative stress. Rationale In many studies, the diversity of views on the influence of mode of delivery on the redox status of neonates is likely to be caused by the use of different biomarkers to measure either the oxidative stress, the antioxidant activity, or both. Furthermore, incomplete explanation for sampling cord blood in these studies, either arterial, venous blood or both, complicates matters. To solve the above, this study was designed to assess the effects of mode of delivery on both pro-oxidants, via d-ROMs, and antioxidants, via BAP, in both umbilical arterial and venous blood samples obtained just after birth. There are no existing studies of BAP in both umbilical arterial and venous blood to which we can refer. In conclusion, our study suggests that the pro-oxidant/antioxidant balance in neonates just after birth is better than may be expected when compared to the potentials of adults (including pregnant mothers) according to interpretations of BAP/d-ROMs. This can be understood that neonates may have already been endowed with the ability to cope with oxidative stress, as informed by high BAP values in both umbilical arterial and venous blood. Vaginal delivery may have an effect on increasing oxidative stress as a result of the stress of labors (as measured by d-ROMs), and an elective cesarean section, which has better BAP/d-ROMs in umbilical venous blood than that of vaginal delivery, may not impair the mother's oxidative stress status.
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Affiliation(s)
- Hisaaki Kobayashi
- a Department of Obstetrics , Nishisaitama Chuo National Hospital , Tokorozawa , Japan.,b Department of Gynecology , Nishisaitama Chuo National Hospital , Tokorozawa , Japan
| | | | - Akihiro Yoshino
- a Department of Obstetrics , Nishisaitama Chuo National Hospital , Tokorozawa , Japan.,b Department of Gynecology , Nishisaitama Chuo National Hospital , Tokorozawa , Japan
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Sandesc M, Rogobete AF, Bedreag OH, Dinu A, Papurica M, Cradigati CA, Sarandan M, Popovici SE, Bratu LM, Bratu T, Stan AT, Sandesc D. Analysis of oxidative stress-related markers in critically ill polytrauma patients: An observational prospective single-center study. Bosn J Basic Med Sci 2018; 18:191-197. [PMID: 29310566 DOI: 10.17305/bjbms.2018.2306] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Revised: 10/08/2017] [Accepted: 10/08/2017] [Indexed: 12/18/2022] Open
Abstract
Critically ill polytrauma patients have increased production of free radicals (FRs) and consequent alterations in biochemical pathways, as well as disruption of cellular integrity, due to increased lipid peroxidation. The aim of this study was to investigate several biomarkers associated with increased oxidative stress in critically ill polytrauma patients, and to evaluate the effect of antioxidant treatment on the clinical outcome in these patients. A total of 67 polytrauma patients from an intensive care unit met the selection criteria. Antiox group included 35/67 patients who received antioxidant therapy, while 32/67 patients without antioxidant treatment were considered as control group. Antioxidant therapy consisted of simultaneous administration of Vitamin C (sodium ascorbate) and N-acetylcysteine, through continuous intravenous infusion. Clinical and paraclinical evaluation of the patients was performed daily until discharge or death. At admission, laboratory parameters did not differ significantly between two groups. At discharge/upon death, statistically significant differences in favor of Antiox group were observed in the following parameters: thrombocytes, activated partial thromboplastin time, prothrombin time, total bilirubin, total cholesterol, high-density lipoproteins, low-density lipoproteins, erythrocyte sedimentation rate, interleukin 6 (all p = 0.0001), total protein (p = 0.0005), serum albumin (p = 0.0004), lactate dehydrogenase (p = 0.0006), and C-reactive protein (p = 0.0014). Starting from day 5, the APACHE II score was significantly decreased in Antiox versus control group (p < 0.05). Finally, the sepsis incidence and mortality rate were significantly lower in Antiox group (p < 0.05). Decreasing the level of oxidative stress by antioxidant substances significantly correlated with a better prognosis and outcome in our patients. Further studies should elucidate more clearly the mechanism of action of antioxidants in critically ill polytrauma patients.
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Affiliation(s)
- Mihai Sandesc
- Faculty of Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.
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Current insights on the role of iron and copper dyshomeostasis in the pathogenesis of bilirubin neurotoxicity. Life Sci 2017; 191:34-45. [PMID: 29030087 DOI: 10.1016/j.lfs.2017.10.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 09/13/2017] [Accepted: 10/09/2017] [Indexed: 01/18/2023]
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Ramy N, Ghany EA, Alsharany W, Nada A, Darwish RK, Rabie WA, Aly H. Jaundice, phototherapy and DNA damage in full-term neonates. J Perinatol 2016; 36:132-6. [PMID: 26583945 DOI: 10.1038/jp.2015.166] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 09/11/2015] [Accepted: 10/01/2015] [Indexed: 01/12/2023]
Abstract
OBJECTIVE Phototherapy is the standard therapeutic approach for neonatal hyperbilirubinemia. Oxidative effects of phototherapy may have potential harms, including DNA damage. Unconjugated bilirubin (UCB) might also possess antigenotoxic potential. Intensive phototherapy is more efficacious than conventional phototherapy in treating hyperbilirubinemia. This study aimed to assess the impact of hyperbilirubinemia and the two different types of phototherapy on DNA damage in peripheral blood mononuclear cells of neonates. STUDY DESIGN The study was conducted on term neonates with non-hemolytic hyperbilirubinemia and control healthy neonates. Genotoxicity was assessed using single-cell gel electrophoresis (Comet assay) in peripheral mononuclear cells. Blood samples were obtained at enrollment in all infants and after intensive or conventional phototherapy in jaundiced infants. RESULT DNA damage did not significantly differ between jaundiced and non-jaundiced neonates (11.4±8.7 and 10.9±8.3 arbitrary units (AU), respectively, P=0.58). It increased significantly after exposure to phototherapy compared with prephototherapy values (45.6±14.7 vs 11.4±8.7 AU, respectively, P<0.001). The duration of phototherapy correlated positively with markers of DNA damage (r=0.86, P<0.001); however, the intensity of used light did not significantly impact genotoxicity. CONCLUSION Hyperbilirubinemia does not influence DNA damage, whereas both conventional and intensive phototherapy are associated with DNA damage in term infants with hyperbilirubinemia.
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Affiliation(s)
- N Ramy
- Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - E A Ghany
- Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - W Alsharany
- Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - A Nada
- Institute of Postgraduate Childhood, Ain Shams University, Cairo, Egypt
| | - R K Darwish
- Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - W A Rabie
- Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - H Aly
- Division of Newborn Services, The George Washington University Medical Center, Washington, DC, USA
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24
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Yamamoto K, Chiba T, Matsumoto T. Effect of tumor necrosis factor-α antagonists on oxidative stress in patients with Crohn’s disease. World J Gastroenterol 2015; 21:10208-10214. [PMID: 26401086 PMCID: PMC4572802 DOI: 10.3748/wjg.v21.i35.10208] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 06/01/2015] [Accepted: 07/15/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate changes in oxidative stress in Crohn’s disease (CD) before and after anti-tumor necrosis factor (TNF)-α treatment.
METHODS: A total of 42 patients with active CD, who were scheduled to be treated by anti-TNF-α antibodies, were enrolled. Serum levels of diacron-reactive oxygen metabolites (d-ROM), biological antioxidant potential (BAP), and modified ratio of oxidative stress and antioxidant capacity (m-OA) were measured using the Free Radical Analytical System before and 8 wk after induction of therapy with infliximab or adalimumab. The values for oxidative stress were correlated with disease activity and clinical response as determined by the CD activity index (CDAI) at 8 and 54 wk after the therapy.
RESULTS: Prior to treatment, d-ROM showed significant correlations with CDAI (r = 0.42, P < 0.01). There was a significant negative correlation between m-OA and CDAI before and after treatment (r = -0.48 vs r = -0.42, P < 0.01). CDAI and d-ROM had decreased significantly by 8 wk after treatment (CDAI; 223.3 ± 113.2 vs 158.3 ± 73.4, P < 0.01, d-ROM; 373 ± 133 vs 312 ± 101, P < 0.05). However, neither BAP nor m-OA had changed significantly. In patients who had responded to the treatment at 8 wk, d-ROM, BAP, and m-OA levels before treatment did not differ significantly between patients with and without loss of response.
CONCLUSION: Anti-TNF-α therapy decreases oxidative stress in patients with CD, but does not alter the production of antioxidants. Dysregulation of antioxidants may be associated with the disease.
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Raicevic S, Eventov-Friedman S, Bolevich S, Selakovic D, Joksimovic J, Djuric J, Globarevic-Vukcevic G, Djuric D, Jakovljevic V. Correlation between oxidative stress and G6PD activity in neonatal jaundice. Mol Cell Biochem 2014; 395:273-9. [PMID: 24997047 DOI: 10.1007/s11010-014-2136-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2014] [Accepted: 06/17/2014] [Indexed: 11/30/2022]
Abstract
Fetal distress represents a pathophysiological condition in which oxygen is not available to the fetus in sufficient quantities. In cases of glucose 6-phosphate dehydrogenase (G6PD) deficiency, under conditions of oxidative stress, the residual G6PD and complimentary antioxidant mechanisms may become insufficient to neutralize the large amounts of ROS and to prevent severe hemolysis. Alteration in the oxidant-antioxidant profile is also known to occur in neonatal jaundice. The study group included 22 neonates presented with fetal distress during labor and 24 neonates with no evidence of fetal distress (control group). Umbilical cord blood samples were taken immediately after delivery, and the following blood tests were carried out after birth and at discharge from the hospital: erythrocyte count, total bilirubin, G6PD activity, and parameters presenting oxidative status [thiobarbituric acid reactive substances (TBARS), NO, O2 (-), H2O2, SOD, CAT, O2 (-)/SOD, and H2O2/CAT]. There were no significant differences in TBARS and NO values among neonates with or without fetal distress. However, the values of O2 (-), H2O2, SOD, O2 (-)/SOD, and H2O2/CAT among neonates born after fetal distress were significantly higher than in neonates without fetal distress (p < 0.01). In neonates with fetal distress, the total number of RBCs at delivery was significantly lower, accompanied with higher bilirubin content. Also neonates with fetal distress had lower activity of G6PD and lower CAT activity. Higher values of oxidative stress parameters in newborns delivered after fetal distress do not indicate strictly what occurred first-oxidative stress or basic lower G6PD activity.
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Affiliation(s)
- S Raicevic
- Clinic of Gynecology and Obstetrics, Clinical Centre of Montenegro, Podgorica, Montenegro
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26
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Becerir C, Kılıç İ, Şahin Ö, Özdemir Ö, Tokgün O, Özdemir B, Akca H. The protective effect of docosahexaenoic acid on the bilirubin neurotoxicity. J Enzyme Inhib Med Chem 2012; 28:801-7. [DOI: 10.3109/14756366.2012.684053] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
| | | | | | | | - Onur Tokgün
- Department of Medical Biology,
Denizli, Turkey
| | - Bülent Özdemir
- Department Anatomy, Pamukkale University Faculty of Medicine,
Denizli, Turkey
| | - Hakan Akca
- Department of Medical Biology,
Denizli, Turkey
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27
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Dadheech G, Sharma P, Gautam S. Oxidative Stress-Induced Response of Some Endogenous Antioxidants in Schizophrenia. Indian J Clin Biochem 2012; 27:278-83. [PMID: 26405388 DOI: 10.1007/s12291-012-0193-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2011] [Accepted: 02/21/2012] [Indexed: 12/29/2022]
Abstract
Reactive oxygen species (ROS) formed in various metabolic reactions cause unlimited damage by attacking and oxidizing the macromolecules. An arsenal of antioxidant substances neutralizes these ROS at various sites of their metabolic cascade, and if disequilibrium exists between the pro and antioxidant system, oxidative stress persists. The present study was undertaken in schizophrenia, to highlight the response and role of some endogenous antioxidants viz. reduced glutathione (GSH), bilirubin, total proteins, albumin and uric acid in scavenging the ROS. The effect of severity of disease, age factor, and substance abuse was also studied. In all, 50 schizophrenics and 50 age and sex-matched controls were enrolled in the present study. Fasting blood samples were drawn for estimating malondialdehyde (MDA), GSH, bilirubin, total proteins, albumin and uric acid in both the groups. The results were statistically analyzed by Z-test and correlated using correlation coefficient (r). The study shows reduction in MDA levels and decline in the level of endogenous antioxidants, but within the normal range. Chronic schizophrenics were at a higher risk of oxidative stress and age and substance abuse seems to worsen the situation.
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Affiliation(s)
- Gora Dadheech
- Department of Biochemistry, NIMS Medical College, Shobha Nagar, Jaipur, Rajasthan
| | - Praveen Sharma
- Department of Biochemistry, Govt. Medical College, Kota, Rajasthan
| | - Shiv Gautam
- Department of Psychiatry, NIMS Medical College, Shobha Nagar, Jaipur, Rajasthan
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28
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El-Abdin MYZ, El-Salam MA, Ibrhim MY, Koraa SS, Mahmoud E. Phototherapy and DNA changes in full term neonates with hyperbilirubinemia. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2012. [DOI: 10.1016/j.ejmhg.2011.11.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022] Open
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29
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Choi SY, Hwang HY, Hong YR, Jung YJ. Clinical Features and Factors Associated with the Frequency of Phototherapy in Premature Birth Gestation < 35 Weeks and Birth Weight ≤2,500 g. KOSIN MEDICAL JOURNAL 2012. [DOI: 10.7180/kmj.2012.27.2.133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Affiliation(s)
- So Yoon Choi
- Department of Pediatrics, College of Medicine, Kosin University, Gospel Hospital, Busan, Korea
| | - Ho Yeon Hwang
- Department of Pediatrics, College of Medicine, Kosin University, Gospel Hospital, Busan, Korea
| | - Yoo Rha Hong
- Department of Pediatrics, College of Medicine, Kosin University, Gospel Hospital, Busan, Korea
| | - Yu Jin Jung
- Department of Pediatrics, College of Medicine, Inje University, Haeundae Paik Hospital, Busan, Korea
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Köksal N, Kavurt AV, Cetinkaya M, Ozarda Y, Ozkan H. Comparison of lipid emulsions on antioxidant capacity in preterm infants receiving parenteral nutrition. Pediatr Int 2011; 53:562-6. [PMID: 21342355 DOI: 10.1111/j.1442-200x.2011.03335.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Although a variety of different lipid emulsions with varying fatty acid contents have been developed, there are some concerns about the administration of these lipid emulsions because of potential adverse effects, including oxidative stress-related morbidity. The aim of the present study was to evaluate and compare the effects of the standard soybean oil-based and olive oil-based i.v. lipid emulsions (ILE) on oxidative stress, determined by total antioxidant capacity (TAC), and to investigate the safety of the use of these two emulsions in terms of biochemical indices. METHODS In this prospective study, premature infants were randomly assigned to two groups, each group consisting of 32 patients who received parenteral ILE of either 20% olive oil or 20% soybean oil. They were given ILE for 7 days and then were evaluated with regard to TAC. RESULTS No statistically significant difference was observed between the groups in terms of routine biochemical parameters. TAC for both groups on day 7 was significantly lower compared with that on day 0. Although the decrease in TAC within 7 days of ILE administration was greater in the soybean group compared with that in the olive oil group, it was not statistically significant. CONCLUSIONS Olive oil-based ILE exhibit similar antioxidant activity and can be used as an alternative to soybean oil-based ILE. TAC significantly decreased in infants following administration of either lipid emulsion, and premature infants tolerated either ILE well, both biochemically and clinically.
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Affiliation(s)
- Nilgün Köksal
- Division of Neonatology, Uludag University School of Medicine, Bursa, Turkey
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Erdem SS, Kurban S, Altunhan H, Annagür A, Örs R, Yerlikaya FH, Gökçe R, Mehmetoğlu İ. Ischaemia-modified albumin levels in newborn jaundice before and after phototherapy. Cell Biochem Funct 2011; 29:521-5. [DOI: 10.1002/cbf.1786] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2011] [Revised: 03/09/2011] [Accepted: 06/06/2011] [Indexed: 11/08/2022]
Affiliation(s)
- S. S. Erdem
- University of Selcuk; Meram Faculty of Medicine; Department of Biochemistry, ; Konya; Turkey
| | - S. Kurban
- University of Selcuk; Meram Faculty of Medicine; Department of Biochemistry, ; Konya; Turkey
| | - H. Altunhan
- University of Selcuk; Meram Faculty of Medicine; Department of Neonatalogy, ; Konya; Turkey
| | - A. Annagür
- University of Selcuk; Meram Faculty of Medicine; Department of Neonatalogy, ; Konya; Turkey
| | - R. Örs
- University of Selcuk; Meram Faculty of Medicine; Department of Neonatalogy, ; Konya; Turkey
| | - F. H. Yerlikaya
- University of Selcuk; Meram Faculty of Medicine; Department of Biochemistry, ; Konya; Turkey
| | - R. Gökçe
- University of Selcuk; Meram Faculty of Medicine; Department of Biochemistry, ; Konya; Turkey
| | - İ. Mehmetoğlu
- University of Selcuk; Meram Faculty of Medicine; Department of Biochemistry, ; Konya; Turkey
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Doğan M, Peker E, Kirimi E, Sal E, Akbayram S, Erel O, Ocak AR, Tuncer O. Evaluation of oxidant and antioxidant status in infants with hyperbilirubinemia and kernicterus. Hum Exp Toxicol 2011; 30:1751-60. [DOI: 10.1177/0960327111401638] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Objective: The objective of the present study was to determine oxidant and antioxidant status in infants with hyperbilirubinemia and/or kernicterus and to find whether there is a relationship between bilirubin level and oxidant/antioxidant status. Patients: The study includes 69 full-term newborns (neonates with hyperbilirubinemia needing phototherapy [Group 1, n = 36] and neonates with kernicterus [Group 2, n = 33]) and 25 age-matched healthy newborn. Results: Plasma total antioxidant capacity (TAC) and serum total oxidant status (TOS) were significantly higher in Groups 1 and 2 than the control group. There was a significant difference between Group 1 and control cases for malondialdehyde (MDA; p < 0.001). Total free sulfhydryl group (TTHI) values were significantly elevated in Group 1 compared to Group 2 and control cases. Correlation analysis showed that the correlation between total bilirubin (TB) and TAC, TOS, MDA and oxidative stress index may be expressed by a quadratic curve. After phototherapy, a statistically significant increase in nitrite level was observed. Conclusion: We demonstrated that the relationship between serum TB and antioxidants and oxidative stress could be expressed by a quadratic correlation curve.
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Affiliation(s)
- Murat Doğan
- Department of Pediatrics, School of Medicine, Yuzuncu Yil University, Van, Turkey
| | - Erdal Peker
- Division of Neonatology, Department of Pediatrics, School of Medicine, Yuzuncu Yil University, Van, Turkey
| | - Ercan Kirimi
- Division of Neonatology, Department of Pediatrics, School of Medicine, Yuzuncu Yil University, Van, Turkey
| | - Ertan Sal
- Department of Pediatrics, School of Medicine, Yuzuncu Yil University, Van, Turkey
| | - Sinan Akbayram
- Department of Pediatrics, School of Medicine, Yuzuncu Yil University, Van, Turkey
| | - Ozcan Erel
- Department of Biochemistry, School of Medicine, Harran University, Sanliurfa, Turkey
| | - Ali Rıza Ocak
- Department of Biochemistry, School of Medicine, Harran University, Sanliurfa, Turkey
| | - Oguz Tuncer
- Division of Neonatology, Department of Pediatrics, School of Medicine, Yuzuncu Yil University, Van, Turkey
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Uras N, Tonbul A, Karadag A, Dogan DG, Erel O, Tatli MM. Prolonged jaundice in newborns is associated with low antioxidant capacity in breast milk. Scandinavian Journal of Clinical and Laboratory Investigation 2010; 70:433-7. [DOI: 10.3109/00365513.2010.506556] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Assessment of DNA damage and plasma catalase activity in healthy term hyperbilirubinemic infants receiving phototherapy. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2009; 680:12-6. [DOI: 10.1016/j.mrgentox.2009.07.016] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2008] [Revised: 06/03/2009] [Accepted: 07/25/2009] [Indexed: 11/19/2022]
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Guven A, Gundogdu G, Uysal B, Cermik H, Kul M, Demirbag S, Ozturk H, Oter S. Hyperbaric oxygen therapy reduces the severity of necrotizing enterocolitis in a neonatal rat model. J Pediatr Surg 2009; 44:534-40. [PMID: 19302854 DOI: 10.1016/j.jpedsurg.2008.06.008] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2008] [Revised: 05/09/2008] [Accepted: 06/15/2008] [Indexed: 11/27/2022]
Abstract
INTRODUCTION Hyperbaric oxygen (HBO) therapy is known to increase oxygen concentration in tissues leading to induction of an adaptive increase in antioxidants, stimulation of angiogenesis, improvement of white blood cell action, and regulation of inflammatory process. Therefore, we tested the potential beneficial effect of HBO in neonatal rat model of necrotizing enterocolitis (NEC). MATERIALS AND METHODS Thirty newborn Sprague-Dawley rats, provided by the Experimental Research Council, Gulhane Military Medical Academy, Ankara,Turkey, were randomly divided into 3 groups as follows: NEC, NEC + HBO, and control. Necrotizing enterocolitis was induced by enteral formula feeding and exposure to hypoxia after cold stress at 4 degrees C and oxygen. The NEC + HBO group received HBO at 2.8 atmosphere absolute (ATA) for 90 minutes daily for 3 days. The pups were killed on the fourth day, and their intestinal tissues were harvested for biochemical and histopathologic analysis. Blood samples were also obtained from the pups. RESULTS The mortality rate was highest in the NEC group (3 pups in the NEC group vs 1 pup in the NEC + HBO group). Malondialdehyde and protein carbonyl content were significantly increased, whereas superoxide dismutase and glutathione peroxidase were significantly decreased in the NEC group. All these changes were similar to control levels in the NEC group by HBO treatment. Nitrate plus nitrite (NO(x)) levels and serum tumor necrosis factor alpha were increased in the NEC group and histopathologic injury score and apoptosis index in the NEC group were significantly higher than in the NEC + HBO group. CONCLUSION Hyperbaric oxygen significantly reduced the severity of NEC in our study.
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Affiliation(s)
- Ahmet Guven
- Department of Pediatric Surgery, Gulhane Military Medical Academy, 06017 Etlik, Ankara, Turkey
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Increased heme oxygenase-1 expression in premature infants with respiratory distress syndrome. Eur J Pediatr 2008; 167:1379-83. [PMID: 18301921 DOI: 10.1007/s00431-008-0673-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2007] [Accepted: 01/15/2008] [Indexed: 10/22/2022]
Abstract
Oxidative stress is known to play an important role in the pathogenesis of certain severe illnesses in preterm infants. The enzyme heme oxygenase-1 (HO-1) participates in cytoprotection against oxygen radical injury. We have previously described the role of HO-1 in physiologic adaptation by demonstrating the induction of HO-1 in healthy mature neonates and asymptomatic preterm infants. Our current aim was to investigate the HO-1 expression in preterm infants with respiratory distress syndrome (RDS). We collected venous blood samples from 28 preterm infants with RDS on the 1st, 3rd and 5th days after birth. The HO-1 mRNA expression was determined by means of a competitive reverse transcriptase PCR technique, and a quantitative blood count was performed on the residual blood sample. A significant increase in HO-1 expression was found in the preterm infants with RDS as compared with both the healthy mature and the asymptomatic premature groups. The elevation was approximately eight-fold. The platelet count displayed a significant negative association with the HO-1 expression, and in the RDS prematures with thrombocytopenia the HO-1 induction was significantly greater than in those with a normal platelet count. In conclusion, the RDS of prematures is accompanied by an elevated HO-1 expression during the first 5 days of life, consistent with the inflammatory and oxidative characteristics of the disease.
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Shortland DB, Hussey M, Dey Chowdhury A. Understanding neonatal jaundice: UK practice and international profile. ACTA ACUST UNITED AC 2008; 128:202-6. [DOI: 10.1177/1466424008092229] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Over the last 25 years there have been considerable advances in the treatment and technologies used in the care of newborn infants. Most of these advances are related to the care of the premature infants and there have been few changes in the management of conditions commonly seen in term infants. Neonatal jaundice is one of the commonest neonatal disorders and has been recognized since early history. Early neonatal jaundice is usually caused by the physiological destruction of red blood cells in the infant and its importance lies in the ability of the bilirubin pigment so produced to cross the blood brain barrier resulting in neurotoxicity. Prolonged neonatal jaundice (after 14 days of age) may be an indication of an underlying liver disorder. The approach to neonatal jaundice has remained largely unchanged over the last two to three decades. We continue to rely on visual inspection to assess the severity of early neonatal jaundice. We have technology that is effective in reducing the level of bilirubinaemia but in the UK there is no clear consensus as to the level at which jaundice should be treated. We do not have a standardized approach to the management of prolonged jaundice and there is potential for infants with significant liver problems to be diagnosed at a relatively late stage. Some countries (for example the US) have professional bodies who have introduced guidelines to ensure a standardized approach to the jaundice infant. We have little information about neonatal jaundice treatment in other parts of the developing world.
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Affiliation(s)
- David B Shortland
- Department of Paediatrics and Child Health, Poole Hospital NHS Trust, Longfleet Road, Poole, Dorset BH15 2JB,
| | - Martin Hussey
- Department of Paediatrics and Child Health, Poole Hospital NHS Trust, Longfleet Road, Poole, Dorset BH15 2JB
| | - Ashoka Dey Chowdhury
- Department of Paediatrics and Child Health, Poole Hospital NHS Trust, Longfleet Road, Poole, Dorset BH15 2JB
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Bjelaković G, Stojanović I, Jevtović-Stoimenov T, Kostić G, Sokolović D, Ilić M, Bjelaković L. Polyamine oxidase activity in peripheral blood of newborn infants with neonatal hyperbilirubinemia: is bilirubin an antioxidant? J Basic Clin Physiol Pharmacol 2008; 19:103-18. [PMID: 19024928 DOI: 10.1515/jbcpp.2008.19.2.103] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
BACKGROUND Neonatal hyperbilirubinemia can be physiological and pathological and most frequently is a consequence of faster erythrocytes (RBC) hemolysis. Free unconjugated bilirubin is a highly toxic compound, especially for the central nervous system. The most abundant polyamines circulating in blood are spermidine (Spd) and spermine (Sp), which are mainly localized in RBC, where they control membrane permeability. Polyamine oxidase (PAO) exerts an important activity in the plasma and erythrocytes of newborn infants with hyperbilirubinemia, catalyzing the oxidative deamination of Sp and Spd, producing potentially toxic agents that induce apoptosis of mammalian cells. The present study investigated polyamine metabolism by measuring PAO activity in the blood of newborn infants with hyperbilirubinemia and explored the possible antioxidant function of bilirubin through monitoring malondialdehyde (MDA) levels. METHODS The study included 43 newborns, 10 in the control and 33 in the diseased group. Blood PAO activity and bilirubin and MDA levels were measured using spectrophotometric methods. RESULTS/DISCUSSION Our results indicate that bilirubin, at physiologic concentrations, protects neonatal erythrocytes against oxidative stress. The positive correlation between PAO activity and MDA levels with high bilirubin concentrations (> 200 micromol/L) in newborn infants indicates that in pathological conditions, bilirubin cannot exert its antioxidant function. CONCLUSION Investigating the function of polyamines in erythrocytes and the importance of PAO related to hemolysis and bilirubin synthesis is necessary to shed light on the functions of PAO and its metabolites on the permeability of the erythrocyte membrane.
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Jangaard KA, Vincer MJ, Allen AC. A randomized trial of aggressive versus conservative phototherapy for hyperbilirubinemia in infants weighing less than 1500 g: Short- and long-term outcomes. Paediatr Child Health 2007; 12:853-8. [PMID: 19043499 PMCID: PMC2532565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/17/2007] [Indexed: 05/27/2023] Open
Abstract
OBJECTIVE Treatment regimens for hyperbilirubinemia vary for very low birth weight infants. The present study seeks to determine whether the initiation of conservative phototherapy is as effective as aggressive phototherapy in reducing peak bilirubin levels without increasing adverse effects. STUDY DESIGN The present randomized, controlled study included infants with birth weights between 500 g and 1500 g, stratified into two birth weight groups. In one group, aggressive phototherapy was commenced by 12 h of age, while in the other group, conservative phototherapy was commenced if serum bilirubin levels exceeded 150 mumol/L. The primary outcome variables were peak serum bilirubin levels and hours of phototherapy. Secondary outcomes were age at peak bilirubin levels, number of infants with rebound hyperbilirubinemia, and number of adverse short- and long-term outcomes. RESULTS Of 174 eligible infants, 95 consented to participate -49 in the conservative arm and 46 in the aggressive arm. Ninety-two infants completed the study. There was no significant difference in peak bilirubin levels except in infants who weighed less than 1000 g -171.2+/-26 mumol/L (conservative) versus 139.2+/-46 mumol/L (aggressive); P<0.02. There was no difference in duration of phototherapy or rebound hyperbilirubinemia. There were no differences in short-term adverse outcomes. Of the 87 infants who survived until hospital discharge, 82 (94%) had some follow-up and 75 (86%) attended follow-up until 18 months corrected age. The incidence of cerebral palsy, abnormal mental developmental index at 18 months corrected age, or combined outcome of cerebral palsy and death did not significantly differ between the two groups. CONCLUSIONS In infants weighing less than 1000 g, peak bilirubin levels were significantly higher using conservative phototherapy regimens and there was a tendency for poor neurodevelopmental outcome.
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Affiliation(s)
- Krista A Jangaard
- Department of Neonatal Pediatrics, Dalhousie University, Halifax, Nova Scotia
| | - Michael J Vincer
- Department of Neonatal Pediatrics, Dalhousie University, Halifax, Nova Scotia
| | - Alexander C Allen
- Department of Neonatal Pediatrics, Dalhousie University, Halifax, Nova Scotia
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Abdul-Razzak KK, Nusier MK, Obediat AD, Salim AM. Antioxidant vitamins and hyperbilirubinemia in neonates. GERMAN MEDICAL SCIENCE : GMS E-JOURNAL 2007; 5:Doc03. [PMID: 19675711 PMCID: PMC2703239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2006] [Indexed: 11/12/2022]
Abstract
OBJECTIVE Low antioxidant system may contribute to the severity of neonatal hyperbilirubinemia. The aim of this research was to explore the relationship between plasma vitamin E and C levels and the severity of hyperbilirubinemia in full-term neonates with normal glucose 6-phosphate dehydrogenase (G6PD) activities. METHODS A total of 130 full-term healthy live birth neonates of healthy mothers with normal G6PD activity were included in this study. In addition to routine blood analysis, plasma total bilirubin, vitamin E and C levels and G6PD activity were measured on the first day of life. None of the neonates was ABO incompatible or anemic. RESULTS Neonates who did not develop hyperbilirubinemia (n=119) had a mean plasma bilirubin level of 65+/-24 micromol/l (median 58.1), while neonates who developed significant hyperbilirubinemia (n=11) had a mean plasma bilirubin level of 238+/-56 micromol/l (median 246.2) on the first day of life. Mean plasma vitamin C levels of neonates who developed hyperbilirubinemia were significantly lower than those who did not develop hyperbilirubinemia (87+/-22 micromol/l (median 89.4) vs. 132+/-36 micromol/l (median 127.7), respectively, P=0.0001). Similar results were observed for plasma vitamin E levels in neonates who did or did not develop hyperbilirubinemia (7.5+/-2 micromol/l (median 6.3) vs. 10.4+/-5 micromol/l (median 9.1), respectively, P=0.001). Hemoglobin and hematocrit were significantly lower in neonates who developed hyperbilirubinemia (P=0.0002 and P=0.0003, respectively), although gestational age and birth weight for the two groups showed no significant difference. CONCLUSION The results of the present work indicate that low level of plasma vitamins C and E are associated with significant hyperbilirubinemia in full-term neonates.
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Affiliation(s)
- Khalid K. Abdul-Razzak
- Department of Clinical Pharmacy, Jordan University of Science and Technology, Faculty of Pharmacy, Irbid, Jordan,*To whom correspondence should be addressed: Khalid K. Abdul-Razzak, Department of Clinical Pharmacy, Jordan University of Science and Technology, Faculty of Pharmacy, P.O Box 3030. Irbid 22110, Jordan, Tel.: 962-2-7201000 Ext. 23536, Fax: 962-2-7201075, E-mail:
| | - Mohamad K. Nusier
- Department of Biochemistry and Molecular Biology, Jordan University of Science and Technology, Faculty of Medicine, Irbid, Jordan
| | - Ahmad D. Obediat
- Department of Pediatrics, Princess Rahma Hospital, Irbid, Jordan
| | - Ahmad M. Salim
- College of Applied Medical Science, Jordan University of Science and Technology, Irbid, Jordan
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Dani C, Bertini G, Cecchi A, Corsini I, Pratesi S, Rubaltelli FF. Association between peak serum bilirubin and severity of respiratory distress syndrome in infants of less than 30 weeks' gestation. J Perinat Med 2007; 35:141-6. [PMID: 17302512 DOI: 10.1515/jpm.2007.023] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Bilirubin can enter the alveolar space where it could inactivate surfactant and act as an anti-oxidant agent. OBJECTIVE To assess the hypothesis that total serum bilirubin level (TSB) may affect the severity of respiratory distress syndrome (RDS) and the need of respiratory supports in preterm infants. STUDY DESIGN We performed a retrospective study of 184 preterm infants with RDS, whose peak TSB had a median value of 194.8 micromol/L (=11.3 mg/dL). This value was used to stratify patients into two groups: neonates who developed low and high TSB (< or = or >194.8 micromol/L, respectively). For each patient the highest values of inspired oxygen fraction (FiO(2)), arterial to alveolar oxygen tension ratio (a/APO(2)), oxygenation index (O.I.), ventilatory index (V.I.), and the need and duration of respiratory supports were recorded. RESULTS Seventy-five infants were included in the low TSB group and 74 were included in the high TSB group. The RDS severity and the need of respiratory supports were similar in both the groups. The first day of life TSB and peak TSB did not correlate with the highest values of FiO(2) and a/APO(2), and the duration of mechanical ventilation. CONCLUSIONS We did not find any correlation between TSB level and RDS severity. We speculate that this result is because the potential inhibiting effect of bilirubin on surfactant function is neutralized by the exogenous surfactant treatment, while its antioxidant effects do not provide appreciable benefits in the lung tissue.
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Affiliation(s)
- Carlo Dani
- Department of Surgical and Medical Critical Care, Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
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Komatsu F, Kudoh H, Kagawa Y. Evaluation of oxidative stress and effectiveness of low-dose glucocorticoid therapy on exacerbation of chronic obstructive pulmonary disease. J Gerontol A Biol Sci Med Sci 2007; 62:459-64. [PMID: 17452743 DOI: 10.1093/gerona/62.4.459] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) and its exacerbation are considered to be related to oxidative stress. We determined the levels of reactive oxygen metabolites (ROM) and a biological antioxidant potential (BAP) in blood before and after the exacerbation. METHODS For these determinations, the Free Radical Analytical System 4 was used. Twenty-one male patients were divided into two groups. RESULTS Group A patients (n = 11, for whom the disease was end-stage) showed high ROM levels and low BAP levels. Meanwhile, Group B patients (n = 10, for whom the disease was not end-stage but the exacerbation was repeated) exhibited variable ROM levels corresponding to the symptoms. Before the exacerbation, ROM levels increased. After administering high-dose glucocorticoids, the exacerbation disappeared and ROM levels decreased to the baseline. To suppress the relapse, the Group B patients were medicated with low-dose glucocorticoids by inhalation and systemic administration. Then, ROM levels did not increase or the relapse did not occur. BAP levels continued to be low, and were restored after a stable state was obtained. CONCLUSION Overproduction of ROM may precede exacerbation of COPD, and the low-dose glucocorticoid therapy may be effective to suppress its overproduction and to preserve COPD in a stable state.
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Affiliation(s)
- Fumio Komatsu
- The High Technology Research Center, Kagawa Nutrition University, Saitama, Japan.
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Makay B, Duman N, Ozer E, Kumral A, Yeşilirmak D, Ozkan H. Randomized, controlled trial of early intravenous nutrition for prevention of neonatal jaundice in term and near-term neonates. J Pediatr Gastroenterol Nutr 2007; 44:354-8. [PMID: 17325557 DOI: 10.1097/mpg.0b013e31802b31f2] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND This study was undertaken to investigate the effects of early parenteral nutrition on prevention of neonatal jaundice in term and near-term neonates who could not be enterally fed. PATIENTS AND METHODS Seventy-two infants were randomized into 2 groups: the early parenteral nutrition group (group 1) received 1.0 g/kg/d amino acids beginning within the first day and 1.0 g/kg/d lipid added the next day. The conventional nutrition group (group 2) started on a solution containing 10% glucose and electrolytes in the first 72 hours of life, followed by 0.5 g/kg/d amino acids and lipid. Amino acids and lipid were each increased by 0.5 g/kg/d to a maximum of 3.0 g/kg/d in both groups. Main outcome measures were energy intake; serum bilirubin levels at 24, 48, and 72 hours; need for phototherapy; and duration of phototherapy. RESULTS Higher energy intake was achieved after the first day in group 1. Daily serum bilirubin levels did not significantly differ between groups. Nine patients in each group required phototherapy. The initiation times of phototherapy were 92.9 hours +/- 25.5 in group 1 and 83.1 hours +/- 28.5 in group 2. Durations of phototherapy were 37.3 hours +/- 11.1 in group 1 and 52.0 hours +/- 20.7 in group 2. There were no significant differences in the requirement, initiation time, and duration of phototherapy. CONCLUSIONS Early parenteral nutrition has no proven benefit in terms of therapy requirement or severity and duration of neonatal jaundice compared with conventional parenteral nutrition in term and near-term infants who could not be enterally fed.
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Affiliation(s)
- Balahan Makay
- Department of Pediatrics, Division of Neonatalogy, Dokuz Eylul University Hospital, Izmir, Turkey.
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Vítek L, Schwertner HA. The Heme Catabolic Pathway and its Protective Effects on Oxidative Stress‐Mediated Diseases. Adv Clin Chem 2007; 43:1-57. [PMID: 17249379 DOI: 10.1016/s0065-2423(06)43001-8] [Citation(s) in RCA: 152] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Bilirubin, the principal bile pigment, is the end product of heme catabolism. For many years, bilirubin was thought to have no physiological function other than that of a waste product of heme catabolism--useless at best and toxic at worst. Although hyperbilirubinemia in neonates has been shown to be neurotoxic, studies performed during the past decade have found that bilirubin has a number of new and interesting biochemical and biological properties. In addition, there is now a strong body of evidence suggesting that bilirubin may have a beneficial role in preventing oxidative changes in a number of diseases including atherosclerosis and cancer, as well as a number of inflammatory, autoimmune, and degenerative diseases. The results also suggest that activation of the heme oxygenase and heme catabolic pathway may have beneficiary effects on disease prevention either through the action of bilirubin or in conjunction with bilirubin. If so, it may be possible to therapeutically induce heme oxygenase, increase bilirubin concentrations, and lower the risk of oxidative stress-related diseases.
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Affiliation(s)
- Libor Vítek
- Fourth Department of Internal Medicine, Institute of Clinical Biochemistry, Laboratory Diagnostics, Charles University of Prague, U Nemocnice 2, Praha 2, 128 08 Prague, Czech Republic
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Muñoz-Hoyos A, Bonillo-Perales A, Avila-Villegas R, González-Ripoll M, Uberos J, Florido-Navío J, Molina-Carballo A. Melatonin levels during the first week of life and their relation with the antioxidant response in the perinatal period. Neonatology 2007; 92:209-16. [PMID: 17519530 DOI: 10.1159/000102957] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2006] [Accepted: 01/30/2007] [Indexed: 11/19/2022]
Abstract
AIM Melatonin is a potent free radical scavenger and an indirect antioxidant. Knowledge about the behavior of melatonin secretion in the early neonatal period, which may relate to its properties at a vital stage during very high antioxidant demands, is limited. PATIENTS AND METHODS We studied 35 newborns admitted to the Neonatal Unit with respiratory distress syndrome (RDS) and with no signs of sepsis, severe anemia, hemodynamic compromise or malformation. The gestational age of the newborns was 26-40 weeks (mean value 32.5 weeks) and the weight at birth was 870-4,400 g (mean value 1,800 g). They were classified into two groups: <or=1,500 g or >1,500 g birthweight. In all cases, at 09:00 h on their 1st, 3rd and 7th days of life, serum melatonin was measured by RIA. The clinical history was recorded and treatment and follow-up were performed according to established neonatology practice, and the resultant data recorded. Informed consent from the parents or guardians was obtained in accordance with the Declaration of Helsinki. Statistical analysis was carried out using ANOVA-II (factor I: day of sample; factor II: birthweight). RESULTS There were significant increases in melatonin levels with increasing birthweight (p = 0.017), but no changes by day of sample. Although in both study groups melatonin levels increased during the first few days this was not statistically significant. CONCLUSIONS In newborns of low birthweight, we report high melatonin concentrations in the morning and during the first week of life. These increase with maturation, and at full-term were similar to nocturnal levels during the acrophase of pineal gland secretion in toddlers and schoolage children, when pineal gland secretion is maximal and takes place reflecting environmental variations. In the early neonatal period these high levels of melatonin seem to derive from extrapineal sources, which mature to provide antioxidant protection in accordance with other elements of the antioxidant network to compensate for the high levels of oxidative stress that are present in the perinatal period.
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Affiliation(s)
- A Muñoz-Hoyos
- Departamento de Pediatría, Hospital Universitario San Cecilio, Granada, Spain
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Collard KJ. Is there a causal relationship between the receipt of blood transfusions and the development of chronic lung disease of prematurity? Med Hypotheses 2005; 66:355-64. [PMID: 16236459 DOI: 10.1016/j.mehy.2005.04.046] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2005] [Accepted: 04/26/2005] [Indexed: 12/16/2022]
Abstract
The number and total volume of blood transfusions received by premature babies is, after gestational age and birth weight a good predictor of the likelihood of developing chronic lung disease of prematurity (CLD) and retinopathy of prematurity (ROP). Oxidative damage, inflammation and pulmonary infections are also strongly associated with the development of CLD. It is currently not clear whether there is a causal relationship between the receipt of blood transfusions and oxidative damage, infection, inflammation and CLD in these babies. Strong arguments may be made both for and against a causal relationship. The babies who receive blood transfusions are usually smaller than those who do not, and are ventilated, often with high oxygen levels, for a longer period of time. The longer the baby is on a ventilator the more likely it is to develop pulmonary infection and inflammation. All these factors will promote free radical production and oxidative damage irrespective of the receipt of blood transfusion. This would argue against a causal relationship. On the other hand, an argument may be presented which is based on iron promoted free radical generation, infection and fibrosis consequent to the breakdown of haeme released from transfused erythrocytes. Haeme is broken down by haeme oxygenase (HO) to iron, CO and bilirubin. Under normal circumstances the products of HO activity are beneficial to the organism, but when HO activity is excessive, the products are potentially damaging. Free iron, (in the Fe2+ form) if not sequestered with protein or urate, will generate highly toxic free radicals via the Fenton and Heber-Wiess reactions, predispose the tissue to infection and promote fibrosis. The iron chelating ability of the premature baby appears to be limited so that it would be difficult to deal with any increase in free iron production. Free iron will in turn induce HO activity leading to a potentially serious positive feedback process. The lung is particularly sensitive to iron induced HO activity. In addition, HO activity may be enhanced by other events occurring in the premature lung such as the production of proinflammatory cytokines and the reduced level of glutathione. Thus, the possibility of a causal relationship clearly exists and needs to be examined. This can be attempted by measuring the products of HO activity in relation to the receipt of blood transfusions.
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Affiliation(s)
- Keith J Collard
- University of Plymouth, School of Health Professions, Millbrook House Site, Millbrook Lane, Topsham Road, Exeter, Devon EX2 6ES, UK.
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Abstract
The presence of yellow staining and damage to the brain caused by unconjugated bilirubin was first described by Hervieux in 1847. Kernicterus, the technical term used to describe the intense yellow staining in the basal ganglia of the brain, was first used by Schmorl in 1903. Perhaps as many as 60 percent of all babies born each year in the U.S. are diagnosed with clinical jaundice. Kernicterus is a preventable brain injury caused by severe jaundice, yet it remains a threat today. Because of this, anyone caring for newborns must be aware of the risks and treatment for hyperbilirubinemia and the sequelae of this seemingly benign entity.
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Dani C, Masini E, Bertini G, di Felice AM, Pezzati M, Ciofini S, Rossetti M, Gallori G, Ciuti R, Buonocore G, Paffetti P, Mannaioni PF, Rubaltelli FF. Role of heme oxygenase and bilirubin in oxidative stress in preterm infants. Pediatr Res 2004; 56:873-7. [PMID: 15470195 DOI: 10.1203/01.pdr.0000145281.12853.9e] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
In a previous study, it was found that the decrease in the total plasma bilirubin level (Btot) in preterm infants was associated with the decrease in oxidative stress. We hypothesized that this occurs as a result of a pro-oxidant effect of heme oxygenase (HO), which outcompetes with the antioxidant properties of bilirubin. In this study we studied 12 preterm infants in whom the plasma levels of Btot, total hydroperoxide (TH), protein SH groups, HO activity, non-transferrin-bound iron (NTBI), and erythrocyte CuZn superoxide dismutase (CuZn SOD) activity were concurrently measured when the Btot was >220 microM and after a Btot drop of >34 microM. The Btot decrease was concurrent with the TH decrease, protein SH groups increase, and the HO and CuZn SOD activity increase and was not associated with an NTBI increase. We concluded that 1) Btot does not exert a meaningful antioxidant effect in vivo; 2) HO does not exert a pro-oxidant effect involving an NTBI increase and that, on the contrary, it could exert an antioxidant effect; and 3) the concurrent HO and CuZn SOD activity increase could indicate a synergic antioxidant effect of the two enzymes.
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Affiliation(s)
- Carlo Dani
- Department of Surgical and Medical Critical Care, Section of Neonatology, Careggi University Hospital of Florence, 50134 Florence, Italy. cddni@.unifi.it
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Turgut M, Başaran O, Cekmen M, Karataş F, Kurt A, Aygün AD. Oxidant and antioxidant levels in preterm newborns with idiopathic hyperbilirubinaemia. J Paediatr Child Health 2004; 40:633-7. [PMID: 15469533 DOI: 10.1111/j.1440-1754.2004.00489.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVES Newborns, particularly preterm infants, have limited antioxidant protective capacity. The organism's defence system against reactive oxygen species including vitamins A, E and C, trace element selenium (Se) and enzymes, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) are essential components of the antioxidant system against the oxidative injury to the cellular membranes of erythrocytes. In this study, our aim was to compare the oxidant nitric oxide (total plasma nitrite level as an indicator of nitric oxide (NO)), antioxidant vitamins and selenium and erythrocyte antioxidant enzymes in premature babies with hyperbilirubinaemia with healthy preterms. METHODS Twenty preterm infants with newborn jaundice were included in the study group, while 15 preterm infants without jaundice were enrolled in the control group. We evaluated the mean plasma levels of, respectively, the total nitrite as an indicator of NO, bilirubin, vitamins A, E, C and selenium, and the activity of erythrocyte antioxidant enzymes such as CAT, SOD and GSH-Px of preterm infants with idiopathic hyperbilirubinaemia and compared to those of the control group. RESULTS The mean plasma total nitrite and total serum bilirubin levels and blood reticulocyte counts of the study group were found to be significantly higher than those of the control group (P < 0.001, P < 0.001 and P < 0.05, respectively). Furthermore, the activity of erythrocyte antioxidant enzymes (all P < 0.001) and the mean plasma levels of the antioxidant vitamins A, E, and C (P < 0.05, P < 0.05 and P < 0.001, respectively) and selenium (P < 0.001) of the study group were all found to be significantly lower than those of the control group. CONCLUSION We hypothesize that low antioxidants in pretem babies may predispose them to increased oxidative stress, and cause hyperbilirubinaemia.
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Affiliation(s)
- M Turgut
- Faculty of Medicine, Firat University, Elazig, Turkey.
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Brito MA, Brites D, Butterfield DA. A link between hyperbilirubinemia, oxidative stress and injury to neocortical synaptosomes. Brain Res 2004; 1026:33-43. [PMID: 15476695 DOI: 10.1016/j.brainres.2004.07.063] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/31/2004] [Indexed: 11/28/2022]
Abstract
Cytotoxicity by unconjugated bilirubin involves disturbances of membrane structure, excitotoxicity and cell death. These events were reported to trigger elevated free radicals production and impairment of calcium homeostasis, and to result in loss of cell membrane integrity. Therefore, this study was designed to investigate whether interaction of clinically relevant concentrations of free unconjugated bilirubin with synaptosomal membrane vesicles could be linked to oxidative stress, cytosolic calcium accumulation and perturbation of membrane function. Synaptosomal vesicles were prepared from gerbil cortical brain tissue and incubated with purified bilirubin (<or=1 microM), for 4 h at 37 degrees C. Intracellular concentrations of reactive oxygen species (ROS) and calcium were determined by dichlorofluorescin and BAPTA fluorescent probes, respectively. Membrane protein and lipid oxidation were evaluated by immunocytochemistry and phosphatidylserine exposure by annexin V binding. Levels of reduced and oxidized glutathione (GSH and GSSG, respectively), as well as activities of Mg(2+)-ATPase aminophospholipid translocase (flippase) and Na(+),K(+)-ATPase, were also measured. Our results showed that bilirubin induced oxidative stress, due to a rise in lipid (>or=10%, P<0.05) and protein oxidation (>or=20%, P<0.01), ROS content (approximately 17%, P<0.01), and a decrease in GSH/GSSG ratio (>30%, P<0.01). In addition, synaptosomes exposed to bilirubin exhibited increased externalization of phosphatidylserine (approximately 10%, P<0.05), together with decreased flippase and NA(+),K(+)-ATPase (>or=15%, P<0.05) activities, events that were accompanied by enhanced intracellular calcium levels ( approximately 20%, P<0.01). The data obtained point out that interaction of unconjugated bilirubin with synaptosomal membrane vesicles leads to oxidative injury, loss of membrane asymmetry and functionality, and calcium intrusion, thus potentially contributing to the pathogenesis of encephalopathy by hyperbilirubinemia.
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Affiliation(s)
- Maria Alexandra Brito
- Centro de Patogénese Molecular--UBMBE, Faculdade de Farmácia, University of Lisbon, Av. das Forças Armadas, 1600-083 Lisbon, Portugal.
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