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Essawy AE, Bekheet GJ, Abdel Salam S, Alhasani RH, Abd Elkader HTAE. Betaine alleviates deficits in motor behavior, neurotoxic effects, and neuroinflammatory responses in a rat model of demyelination. Toxicol Rep 2025; 14:101974. [PMID: 40129881 PMCID: PMC11930798 DOI: 10.1016/j.toxrep.2025.101974] [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: 12/22/2024] [Revised: 02/18/2025] [Accepted: 02/20/2025] [Indexed: 03/26/2025] Open
Abstract
Multiple sclerosis (MS) is characterized as a chronic inflammatory demyelinating neurodegenerative disorder that leads to the deterioration of the myelin sheath and the loss of axons. Betaine, a trimethylglycine compound, is recognized for its ability to penetrate the blood-brain barrier (BBB) and exhibits properties that are antioxidant, anti-inflammatory, and neuroprotective. The cuprizone (CPZ) model serves as an effective tool for investigating the processes of demyelination and remyelination associated with MS. In our research, we examined the protective and therapeutic effects of betaine in a rat model of MS induced by CPZ. The experimental protocol involved administering 600 mg/kg of CPZ orally for 7 days, followed by 2 weeks with 200 mg/kg of CPZ. The protective group received a combination of betaine (1 g/kg/day, orally) and CPZ (200 mg/kg/day), while the therapeutic group was treated with CPZ (600 mg/kg) alongside betaine for three weeks. Behavioral assessments were conducted using inverted screen and rotarod tests to measure balance, motor coordination, and grasping ability. Following these evaluations, the rats were euthanized for analysis of oxidative stress and inflammatory biomarkers, toluidine blue staining, transmission electron microscopy (TEM) imaging, and myelin basic protein (MBP) immunostaining of the corpus callosum (CC). The results indicated that betaine significantly enhanced balance, motor coordination, and grasping ability, while decreasing oxidative stress, inhibiting interleukin (IL)-4 and IL-17 levels, and reversing the demyelination caused by CPZ. Notably, betaine also mitigated the increase in homocysteine (Hcy) levels and facilitated remyelination, evidenced by the presence of normal compacted myelin and increased expression of MBP in the CC. This study substantiates the remyelinating effects of betaine in the context of CPZ-induced demyelination. It suggests that it may contribute to the repair of myelin through the modulation of behavioral deficits, oxidative stress, neuroinflammation, ultrastructural changes, and MBP expression levels, indicating its potential as a complementary therapeutic agent in the management of MS.
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Affiliation(s)
- Amina E. Essawy
- Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Gihad Jamal Bekheet
- Euro-Mediterranean Master in Neuroscience and Biotechnology, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Sherine Abdel Salam
- Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt
- Department of Biological Sciences, Faculty of Science, King Faisal University, P.O. Box 380, Al-Ahsa 31982, Saudi Arabia
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Song GY, Yu QH, Xing XK, Fan XM, Xu SG, Zhang WB, Wu YY, Zhang N, Chao TZ, Wang F, Ding CS, Guo CY, Ma L, Sun CY, Duan SY, Xu P. The YTHDC1 reader protein recognizes and regulates the lncRNA MEG3 following its METTL3-mediated m 6A methylation: a novel mechanism early during radiation-induced liver injury. Cell Death Dis 2025; 16:127. [PMID: 39994235 PMCID: PMC11850776 DOI: 10.1038/s41419-025-07417-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 12/20/2024] [Accepted: 01/31/2025] [Indexed: 02/26/2025]
Abstract
While apoptotic cell death is known to be central to the pathogenesis of radiation-induced liver injury (RILI), the mechanistic basis for this apoptotic activity remains poorly understood. N6-methyladenosine (m6A) modifications are the most common form of reversible methylation observed on lncRNAs in eukaryotic cells, with their presence leading to pronounced changes in the activity of a range of biological processes. The degree to which m6A modification plays a role in the induction of apoptotic cell death in response to ionizing radiation (IR) in the context of RILI remains to be established. Here, IR-induced apoptosis was found to significantly decrease the levels of m6A present, with a pronounced decrease in the expression of methyltransferase-like 3 (METTL3) at 2 d post radiation in vitro. From a mechanistic perspective, a methylated RNA immunoprecipitation assay found that lncRNA MEG3 was a major METTL3 target. The expression of MEG3 was upregulated via METTL3-mediated m6A in a process that was dependent on YTHDC1, ultimately reversing the miR-20b-mediated inhibition of BNIP2 expression. Together, these findings demonstrate that the responsivity of METTL3 activity to IR plays a role in IR-induced apoptotic cell death, leading to the reverse of miR-20b-mediated BNIP2 inhibition through the YTHDC1-dependent m6A modification of MEG3, suggesting that this process may play a central role in RILI incidence.
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Affiliation(s)
- Gui-Yuan Song
- Laboratory of Radiation-induced Diseases and Molecule-targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
- School of Pharmacy, Weifang Medical University, Weifang, Shandong, China
| | - Qing-Hua Yu
- Laboratory of Radiation-induced Diseases and Molecule-targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
- School of Public Health, Weifang Medical University, Weifang, Shandong, China
| | - Xue-Kun Xing
- School of Public Health, Guilin Medical University, Guilin, Guangxi, China
| | - Xin-Ming Fan
- Department of Radiotherapy, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China
| | - Si-Guang Xu
- Key Laboratory of Medical Tissue Regeneration of Henan Province, Xinxiang Medical University, Xinxiang, Henan, China
| | - Wen-Bo Zhang
- Key Laboratory of Medical Tissue Regeneration of Henan Province, Xinxiang Medical University, Xinxiang, Henan, China
| | - Yao-Yao Wu
- Laboratory of Radiation-induced Diseases and Molecule-targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Nan Zhang
- Laboratory of Radiation-induced Diseases and Molecule-targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Tian-Zhu Chao
- Laboratory of Radiation-induced Diseases and Molecule-targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Fei Wang
- Laboratory of Radiation-induced Diseases and Molecule-targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Cheng-Shi Ding
- Laboratory of Radiation-induced Diseases and Molecule-targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Cun-Yang Guo
- Laboratory of Radiation-induced Diseases and Molecule-targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
- School of Public Health, Binzhou Medical University, Yantai, Shandong, China
| | - Li Ma
- Department of Radiotherapy, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China
| | - Chang-Ye Sun
- Key Laboratory of Medical Tissue Regeneration of Henan Province, Xinxiang Medical University, Xinxiang, Henan, China
| | - Shu-Yan Duan
- Laboratory of Radiation-induced Diseases and Molecule-targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Ping Xu
- Laboratory of Radiation-induced Diseases and Molecule-targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China.
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Demyashkin G, Koryakin S, Parshenkov M, Skovorodko P, Vadyukhin M, Uruskhanova Z, Stepanova Y, Shchekin V, Mirontsev A, Rostovskaya V, Ivanov S, Shegay P, Kaprin A. Morphofunctional Features of Glomeruli and Nephrons After Exposure to Electrons at Different Doses: Oxidative Stress, Inflammation, Apoptosis. Curr Issues Mol Biol 2024; 46:12608-12632. [PMID: 39590342 PMCID: PMC11593091 DOI: 10.3390/cimb46110748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 10/27/2024] [Accepted: 11/05/2024] [Indexed: 11/28/2024] Open
Abstract
Kidney disease has emerged as a significant global health issue, projected to become the fifth-leading cause of years of life lost by 2040. The kidneys, being highly radiosensitive, are vulnerable to damage from various forms of radiation, including gamma (γ) and X-rays. However, the effects of electron radiation on renal tissues remain poorly understood. Given the localized energy deposition of electron beams, this study seeks to investigate the dose-dependent morphological and molecular changes in the kidneys following electron irradiation, aiming to address the gap in knowledge regarding its impact on renal structures. The primary aim of this study is to conduct a detailed morphological and molecular analysis of the kidneys following localized electron irradiation at different doses, to better understand the dose-dependent effects on renal tissue structure and function in an experimental model. Male Wistar rats (n = 75) were divided into five groups, including a control group and four experimental groups receiving 2, 4, 6, or 8 Gray (Gy) of localized electron irradiation to the kidneys. Biochemical markers of inflammation (interleukin-1 beta [IL-1β], interleukin-6 [IL-6], interleukin-10 [IL-10], tumor necrosis factor-alpha [TNF-α]) and oxidative stress (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione [GSH]) were measured, and morphological changes were assessed using histological and immunohistochemical techniques (TUNEL assay, caspase-3). The study revealed a significant dose-dependent increase in oxidative stress, inflammation, and renal tissue damage. Higher doses of irradiation resulted in increased apoptosis, early stages of fibrosis (at high doses), and morphological changes in renal tissue. This study highlights the dose-dependent effects of electrons on renal structures, emphasizing the need for careful consideration of the dosage in clinical use to minimize adverse effects on renal function.
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Affiliation(s)
- Grigory Demyashkin
- Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia
- Laboratory of Histology and Immunohistochemistry, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St., 8/2, 119048 Moscow, Russia; (M.P.)
| | - Sergey Koryakin
- Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia
| | - Mikhail Parshenkov
- Laboratory of Histology and Immunohistochemistry, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St., 8/2, 119048 Moscow, Russia; (M.P.)
| | - Polina Skovorodko
- Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia
| | - Matvey Vadyukhin
- Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia
| | - Zhanna Uruskhanova
- Laboratory of Histology and Immunohistochemistry, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St., 8/2, 119048 Moscow, Russia; (M.P.)
| | - Yulia Stepanova
- Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia
| | - Vladimir Shchekin
- Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia
- Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St., 6, 117198 Moscow, Russia
| | - Artem Mirontsev
- Laboratory of Histology and Immunohistochemistry, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St., 8/2, 119048 Moscow, Russia; (M.P.)
| | - Vera Rostovskaya
- Laboratory of Histology and Immunohistochemistry, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St., 8/2, 119048 Moscow, Russia; (M.P.)
| | - Sergey Ivanov
- Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia
| | - Petr Shegay
- Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia
| | - Andrei Kaprin
- Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia
- Department of Urology and Operative Nephrology, Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St., 6, 117198 Moscow, Russia
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Zhou M, Li TS, Abe H, Akashi H, Suzuki R, Bando Y. Expression levels of K ATP channel subunits and morphological changes in the mouse liver after exposure to radiation. World J Exp Med 2024; 14:90374. [PMID: 38948415 PMCID: PMC11212743 DOI: 10.5493/wjem.v14.i2.90374] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 01/28/2024] [Accepted: 03/27/2024] [Indexed: 06/19/2024] Open
Abstract
BACKGROUND ATP sensitive K+ (KATP) channels are ubiquitously distributed in various of cells and tissues, including the liver. They play a role in the pathogenesis of myocardial and liver ischemia. AIM To evaluate the radiation-induced changes in the expression of KATP channel subunits in the mouse liver to understand the potential role of KATP channels in radiation injury. METHODS Adult C57BL/6 mice were randomly exposed to γ-rays at 0 Gy (control, n = 2), 0.2 Gy (n = 6), 1 Gy (n = 6), or 5 Gy (n = 6). The livers were removed 3 and 24 h after radiation exposure. Hematoxylin and eosin staining was used for morphological observation; immunohistochemical staining was applied to determine the expression of KATP channel subunits in the liver tissue. RESULTS Compared with the control group, the livers exposed to 0.2 Gy γ-ray showed an initial increase in the expression of Kir6.1 at 3 h, followed by recovery at 24 h after exposure. Exposure to a high dose of 5.0 Gy resulted in decreased expression of Kir6.1 and increased expression of SUR2B at 24 h. However, the expression of Kir6.2, SUR1, or SUR2A had no remarkable changes at 3 and 24 h after exposure to any of these doses. CONCLUSION The expression levels of Kir6.1 and SUR2B in mouse liver changed differently in response to different radiation doses, suggesting a potential role for them in radiation-induced liver injury.
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Affiliation(s)
- Ming Zhou
- Department of Anatomy, Akita University Graduate School of Medicine, Akita 010-8543, Japan
| | - Tao-Sheng Li
- Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan
| | - Hiroshi Abe
- Sendai Old Age Refresh Station, A Long-term Care Health Facility, Sendai 981-1105, Japan
| | - Hideo Akashi
- Department of Anatomy, Akita University Graduate School of Medicine, Akita 010-8543, Japan
| | - Ryoji Suzuki
- Department of Anatomy, Akita University Graduate School of Medicine, Akita 010-8543, Japan
| | - Yoshio Bando
- Department of Anatomy, Akita University Graduate School of Medicine, Akita 010-8543, Japan
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Khateeb S, Taha EFS. Comparative study of the anti-inflammatory activity of etoricoxib and Matcha green tea against acute kidney injury induced by gamma radiation in rats. Int J Radiat Biol 2024; 100:940-964. [PMID: 38647648 DOI: 10.1080/09553002.2024.2338515] [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: 11/01/2023] [Accepted: 03/25/2024] [Indexed: 04/25/2024]
Abstract
PURPOSE The primary objective of this study was to conduct a comparative analysis of the anti-inflammatory activity between Etoricoxib (ETO) and Matcha green tea (MG) in the context of acute kidney injury (AKI) induced by ionizing gamma radiation (IR) in female rats. Furthermore, the potential impact of whole body IR exposure on the intestinal system and serum estradiol levels was investigated. Additionally, it was acknowledged that the ETO and MG treatments might have exerted favorable effects on the intestinal and hormonal responses. MATERIALS AND METHODS Six groups of rats were assigned to different treatments: control, ETO, MG, irradiation (IRR), ETO + IRR, and MG + IRR. The evaluation included measuring the total phenolic and flavonoid contents of ETO and MG, as well as assessing their antioxidant activity, radical scavenging capacity, reducing power, and total antioxidant capacity. Kidney function was assessed through serum creatinine and urea levels. Oxidative stress markers, including superoxide dismutase, glutathione, malondialdehyde, and catalase, were measured to evaluate the antioxidant effects of ETO and MG. The anti-inflammatory potential of the treatments was evaluated by measuring STAT-3 and interleukins (IL-6, IL-23, and IL-17) using an ELISA assay. Prostaglandin E2 receptor (PGE-2) mRNA expression, histopathological examination, and immunohistochemistry for NF-κB inhibitors were performed to investigate the underlying mechanisms in kidney tissue homogenates. Histopathological changes and DNA fragmentation in the intestinal tissues were determined, and the characterization of Matcha green tea was performed using liquid chromatography-mass spectrometry (LC-MS). This allowed for the identification and quantification of various compounds present in Matcha green tea. Furthermore, the study assessed the effect of IR and treatments on estrogen levels in female rats. RESULTS Data showed that both ETO and MG had the potential to mitigate the adverse effects of AKI induced by IR. Notably, MG exhibited greater efficacy in attenuating oxidative stress and inflammation associated with renal injury. These findings revealed and compared the effects of ETO and MG in alleviating AKI caused by IR. MG demonstrated greater anti-inflammatory and antioxidant properties, highlighting its potential as a natural therapeutic agent. CONCLUSIONS These results contribute to the growing evidence supporting the use of MG in managing IR-induced renal complications. Future studies should focus on elucidating the molecular mechanisms and optimizing the application of MG in clinical settings.
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Affiliation(s)
- Sahar Khateeb
- Biochemistry Division, Department of Chemistry, Faculty of Science, Fayoum University, Fayoum, Egypt
- Department of Biochemistry, Faculty of Science, University of Tabuk, Saudi Arabia
| | - Eman F S Taha
- Health Radiation Research Department, National Centre for Radiation Research and Technology, Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt
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Yang ZJ, Huang SY, Zhong KY, Huang WG, Huang ZH, He TT, Yang MT, Wusiman M, Zhou DD, Chen S, Huang BX, Luo XL, Li HB, Zhu HL. Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m 6A-YTHDF2-dependent manner. Redox Biol 2024; 69:103026. [PMID: 38184996 PMCID: PMC10808937 DOI: 10.1016/j.redox.2024.103026] [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: 12/04/2023] [Revised: 12/25/2023] [Accepted: 01/01/2024] [Indexed: 01/09/2024] Open
Abstract
Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 μg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1β, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1β. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.
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Affiliation(s)
- Zhi-Jun Yang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Si-Yu Huang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Kai-Yi Zhong
- Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Wen-Ge Huang
- Center of Experimental Animals, Sun Yat-sen University, Guangzhou, 510080, China
| | - Zi-Hui Huang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Tong-Tong He
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Meng-Tao Yang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Maierhaba Wusiman
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Dan-Dan Zhou
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Si Chen
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Bi-Xia Huang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Xiao-Lin Luo
- Experimental and Teaching Center for Public Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Hua-Bin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Hui-Lian Zhu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.
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Hu Z, Zhao Y, Jiang J, Li W, Su G, Li L, Ran J. Exosome-derived miR-142-5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB. ENVIRONMENTAL TOXICOLOGY 2023. [PMID: 37209404 DOI: 10.1002/tox.23813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 03/29/2023] [Accepted: 04/16/2023] [Indexed: 05/22/2023]
Abstract
BACKGROUND This study aims to explore the effect of liver stem cells (LSCs)-derived exosomes and the miR-142a-5p carried by them on the process of fibrosis by regulating macrophages polarization. METHODS In this study, CCL4 was used to establish liver fibrosis model. The morphology and purity of exosomes (EVs) were verified by transmission electron microscopy, western blotting (WB) and nanoparticle tracing analysis (NTA). Real-time quantitative PCR (qRT-PCR), WB and enzyme-linked immunoadsorption (ELISA) were used to detect liver fibrosis markers, macrophage polarization markers and liver injury markers. Histopathological assays were used to verify the liver injury morphology in different groups. The cell co-culture model and liver fibrosis model were constructed to verify the expression of miR-142a-5p and ctsb. RESULTS Immunofluorescence of LSCs markers CK-18, epithelial cell adhesion molecule (EpCam), and AFP showed that these markers were up-regulated in LSCs. In addition, we evaluated the ability of LSCs to excrete EVs by labeling LSCs-EVs with PKH67. We found that CCL4 and EVs were simultaneously treated at 50 and 100 μg doses, and both doses of EVs could reduce the degree of liver fibrosis in mice. We tested markers of M1 or M2 macrophage polarization and found that EVs reduced M1 marker expression and promoted M2 marker expression. Further, ELISA was used to detect the secreted factors related to M1 and M2 in tissue lysates, which also verified the above views. Further analysis showed that the expression of miR-142a-5p increased significantly with the increase of EVs treatment concentration and time. Further, in vitro and in vivo LSCs-EVs regulate macrophage polarization through miR-142a-5p/ctsb pathway and affect the process of liver fibrosis. CONCLUSION Our data suggest that EVs-derived miR-142-5p from LSCs improves the progression of liver fibrosis by regulating macrophage polarization through ctsb.
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Affiliation(s)
- Zongqiang Hu
- First People's Hospital of Kunming City, Kunming, China
- The Calmette Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yingpeng Zhao
- First People's Hospital of Kunming City, Kunming, China
- The Calmette Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jie Jiang
- First People's Hospital of Kunming City, Kunming, China
- The Calmette Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Wang Li
- First People's Hospital of Kunming City, Kunming, China
- The Calmette Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Gang Su
- First People's Hospital of Kunming City, Kunming, China
- The Calmette Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Li Li
- First People's Hospital of Kunming City, Kunming, China
- The Calmette Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jianghua Ran
- First People's Hospital of Kunming City, Kunming, China
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Mansour LAH, Elshopakey GE, Abdelhamid FM, Albukhari TA, Almehmadi SJ, Refaat B, El-Boshy M, Risha EF. Hepatoprotective and Neuroprotective Effects of Naringenin against Lead-Induced Oxidative Stress, Inflammation, and Apoptosis in Rats. Biomedicines 2023; 11:biomedicines11041080. [PMID: 37189698 DOI: 10.3390/biomedicines11041080] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 03/28/2023] [Accepted: 03/29/2023] [Indexed: 04/07/2023] Open
Abstract
Naringenin (NRG) is one of the most important naturally occurring flavonoids, predominantly found in some edible fruits, such as citrus species and tomatoes. It has several biological activities, such as antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic, and cardioprotective effects. The heavy metal lead is toxic and triggers oxidative stress, which causes toxicity in many organs, including the liver and brain. This study explored the potential protective role of NRG in hepato- and neurotoxicity caused by lead acetate in rats. Four groups of ten male albino rats were included: group 1 was a control, group 2 was orally treated with lead acetate (LA) at a dose of 500 mg/kg BW, group 3 was treated with naringenin (NRG) at a dose of 50 mg/kg BW, and group 4 was treated with 500 mg/kg LA and 50 mg/kg NRG for 4 weeks. Then, blood was taken, the rats were euthanized, and liver and brain tissues were collected. The findings revealed that LA exposure induced hepatotoxicity with a significant increase in liver function markers (p < 0.05). In addition, albumin and total protein (TP) and the albumin/globulin ratio (A/G ratio) (p < 0.05) were markedly lowered, whereas the serum globulin level (p > 0.05) was unaltered. LA also induced oxidative damage, demonstrated by a significant increase in malonaldehyde (MDA) (p < 0.05), together with a pronounced antioxidant system reduction (SOD, CAT, and GSH) (p < 0.05) in both liver and brain tissues. Inflammation of the liver and brain caused by LA was indicated by increased levels of nuclear factor kappa beta (NF-κβ) and caspase-3, (p < 0.05), and the levels of B-cell lymphocyte-2 (BCL-2) and interleukin-10 (IL-10) (p < 0.05) were decreased. Brain tissue damage induced by LA toxicity was demonstrated by the downregulation of the neurotransmitters norepinephrine (NE), dopamine (DA), serotonin (5-HT), and creatine kinase (CK-BB) (p < 0.05). Additionally, the liver and brain of LA-treated rats displayed notable histopathological damage. In conclusion, NRG has potential hepato- and neuroprotective effects against lead acetate toxicity. However, additional research is needed in order to propose naringenin as a potential protective agent against renal and cardiac toxicity mediated by lead acetate.
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Affiliation(s)
- Lubna A. H. Mansour
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Gehad E. Elshopakey
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Fatma M. Abdelhamid
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Talat A. Albukhari
- Department of Immunology and Hematology, Faculty of Medicine, Umm Al-Qura University, Makkah P.O. Box 6165, Saudi Arabia
| | - Samah J. Almehmadi
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia
| | - Bassem Refaat
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia
| | - Mohamed El-Boshy
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Engy F. Risha
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
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9
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Zhou YJ, Tang Y, Liu SJ, Zeng PH, Qu L, Jing QC, Yin WJ. Radiation-induced liver disease: beyond DNA damage. Cell Cycle 2023; 22:506-526. [PMID: 36214587 PMCID: PMC9928481 DOI: 10.1080/15384101.2022.2131163] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/05/2022] [Accepted: 09/08/2022] [Indexed: 11/03/2022] Open
Abstract
Radiation-induced liver disease (RILD), also known as radiation hepatitis, is a serious side effect of radiotherapy (RT) for hepatocellular carcinoma. The therapeutic dose of RT can damage normal liver tissue, and the toxicity that accumulates around the irradiated liver tissue is related to numerous physiological and pathological processes. RILD may restrict treatment use or eventually deteriorate into liver fibrosis. However, the research on the mechanism of radiation-induced liver injury has seen little progress compared with that on radiation injury in other tissues, and no targeted clinical pharmacological treatment for RILD exists. The DNA damage response caused by ionizing radiation plays an important role in the pathogenesis and development of RILD. Therefore, in this review, we systematically summarize the molecular and cellular mechanisms involved in RILD. Such an analysis is essential for preventing the occurrence and development of RILD and further exploring the potential treatment of this disease.
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Affiliation(s)
- Ying Jie Zhou
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Yun Tang
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Si Jian Liu
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Peng Hui Zeng
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Li Qu
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Qian Cheng Jing
- The Affiliated Changsha Central Hospital, Department of Otolaryngology Head and Neck Surgery,Hengyang Medical School, University of South China, Changsha, Hunan, China
- Institute of Otolaryngology Head and Neck Surgery, Hengyang Medical School, University of South China, Changsha, Hunan, China
| | - Wen Jun Yin
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
- Department of Clinical Laboratory, Changsha Central Hospital, University of South China, Changsha, Hunan, China
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10
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Kim DS, Lee HJ, Sim DY, Park JE, Park Y, Kim B, Shim B, Kim SH. The underlying hepatoprotective mechanism of PKC#963 in alcohol or carbon tetrachloride induced liver injury via inhibition of iNOS, COX-2, and p-STAT3 and enhancement of SOD and catalase. Phytother Res 2023; 37:505-514. [PMID: 36151597 DOI: 10.1002/ptr.7630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 07/10/2022] [Accepted: 09/05/2022] [Indexed: 11/12/2022]
Abstract
The aim of the present study is to explore the underlying hepatoprotective mechanism of PKC#963, consisting of Pinus koraiensis, Saururus chinensis, and Lycium barbarum in association with acute and chronic liver injury induced by alcohol or carbon tetrachloride (CCl4). Here, PKC#963 significantly suppressed aspartate aminotransferase (AST), alanine aminotransferase (ALT), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2) in CCl4-treated HepG2 cells. Also, PKC#963 significantly suppressed reactive oxygen species (ROS) production in HepG2 cells. Consistently, PKC#963 suppressed the expression of AST, ALT, p-STAT3, iNOS, COX-2, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and α-smooth muscle actin (α-SMA) and increased procaspase 3 in the liver tissues of CCl4 treated rats. In addition, PKC#963 enhanced alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) for alcohol metabolism, superoxide dismutase (SOD), and catalase as antioxidant enzymes and also suppressed AST and ALT in alcohol-treated rats. Furthermore, PKC#963 reduced hepatic steatosis and necrosis in CCl4-treated rats by H&E (Hematoxylin and Eosin) staining. Taken together, these findings highlight evidence that PKC#963 has hepatoprotective potential via inhibition of iNOS, COX-2, and p-STAT3 and enhancement of SOD and catalase.
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Affiliation(s)
- Dong Sub Kim
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Hyo-Jung Lee
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Deok Yong Sim
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Ji Eon Park
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Youngsang Park
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Bonglee Kim
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Bumsang Shim
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Sung-Hoon Kim
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
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11
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Abstract
Liver fibrosis has a high incidence worldwide and is the common pathological basis of many chronic liver diseases. Liver fibrosis is caused by the excessive deposition of extracellular matrix and concomitant collagen accumulation in livers and can lead to the development of liver cirrhosis and even liver cancer. A large number of studies have provided evidence that liver fibrosis can be blocked or even reversed by appropriate medical interventions. However, the antifibrosis drugs with ideal clinical efficacy are still insufficient. The edible plant-derived natural compounds have been reported to exert effective antifibrotic effects with few side-effects, representing a kind of promising source for the treatment of liver fibrosis. In this article, we reviewed the current progress of the natural compounds derived from dietary plants in the treatment of liver fibrosis, including phenolic compounds (capsaicin, chlorogenic acid, curcumin, ellagic acid, epigallocatechin-3-gallate, resveratrol, sinapic acid, syringic acid, vanillic acid and vitamin E), flavonoid compounds (genistein, hesperidin, hesperetin, naringenin, naringin and quercetin), sulfur-containing compounds (S-allylcysteine, ergothioneine, lipoic acid and sulforaphane) and other compounds (betaine, caffeine, cucurbitacin B, lycopene, α-mangostin, γ-mangostin, ursolic acid, vitamin C and yangonin). The pharmacological effects and related mechanisms of these compounds in in-vivo and in-vitro models of liver fibrosis are focused.
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12
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Zhong JG, Lan WT, Feng YQ, Li YH, Shen YY, Gong JH, Zou Z, Hou X. Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats. Front Physiol 2023; 14:1077821. [PMID: 37035670 PMCID: PMC10073564 DOI: 10.3389/fphys.2023.1077821] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 03/03/2023] [Indexed: 04/11/2023] Open
Abstract
Introduction: The microbiota-gut-brain axis plays an important role in the pathophysiology of autism spectrum disorder, but its specific mechanisms remain unclear. This study aimed to explore the associations of changes in neurotransmitters and short-chain fatty acids with alterations in gut microbiota in valproic acid model rats. Methods: The autism model rats were established by prenatal exposure to valproic acid (VPA). The Morris water maze test, open field test, and three-chamber test were conducted to assess the behaviors of rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography-mass spectroscopy was used to identify short-chain fatty acids in fecal samples and neurotransmitters in the prefrontal cortex (PFC). Results: The results showed that 28 bacterial taxa between valproic acid model rats and control rats were identified, and the most differential bacterial taxa in valproic acid model rats and control rats belonged to metagenomic species and Lactobacillus intestinalis. Acetic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid were significantly decreased in the valproic acid model rats compared to those in control rats. Five neurotransmitters (threonine, kynurenine, tryptophan, 5-hydroxyindoleacetic acid, denoted as 5-HIAA, and betaine aldehyde chloride, denoted as BAC) were significantly decreased, whereas betaine was increased in the prefrontal cortex of valproic acid model rats compared to control rats. A variety of neurotransmitters (≥4) were correlated with Pseudomonas, Collisella, and Streptococcus at the genus level, and they were also related to the decrease of short-chain fatty acids. Discussion: According to this study, we can preliminarily infer that gut microbiota or their metabolic productions (such as SCFAs) may influence central neurotransmitter metabolism through related pathways of the gut-brain axis. These results provide microbial and short-chain fatty acid (SCFA) frameworks for understanding the role of the microbiota-gut-brain axis in autism spectrum disorder and shed new light on autism spectrum disorder treatment.
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Affiliation(s)
- Jiu-Gen Zhong
- School of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, China
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Wan-Ting Lan
- School of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, China
| | - Yan-Qing Feng
- School of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, China
| | - Yin-Hua Li
- School of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, China
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Ying-Ying Shen
- School of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, China
| | - Jia-Heng Gong
- School of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, China
| | - Zhi Zou
- School of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, China
- *Correspondence: Zhi Zou, ; Xiaohui Hou,
| | - Xiaohui Hou
- School of Sport and Health, Guangzhou Sport University, Guangzhou, Guangdong, China
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
- *Correspondence: Zhi Zou, ; Xiaohui Hou,
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13
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Li WQ, Liu WH, Qian D, Liu J, Zhou SQ, Zhang L, Peng W, Su L, Zhang H. Traditional Chinese medicine: An important source for discovering candidate agents against hepatic fibrosis. Front Pharmacol 2022; 13:962525. [PMID: 36081936 PMCID: PMC9445813 DOI: 10.3389/fphar.2022.962525] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/28/2022] [Indexed: 12/24/2022] Open
Abstract
Hepatic fibrosis (HF) refers to the pathophysiological process of connective tissue dysplasia in the liver caused by various pathogenic factors. Nowadays, HF is becoming a severe threat to the health of human being. However, the drugs available for treating HF are limited. Currently, increasing natural agents derived from traditional Chinese medicines (TCMs) have been found to be beneficial for HF. A systemic literature search was conducted from PubMed, GeenMedical, Sci-Hub, CNKI, Google Scholar and Baidu Scholar, with the keywords of "traditional Chinese medicine," "herbal medicine," "natural agents," "liver diseases," and "hepatic fibrosis." So far, more than 76 natural monomers have been isolated and identified from the TCMs with inhibitory effect on HF, including alkaloids, flavones, quinones, terpenoids, saponins, phenylpropanoids, and polysaccharides, etc. The anti-hepatic fibrosis effects of these compounds include hepatoprotection, inhibition of hepatic stellate cells (HSC) activation, regulation of extracellular matrix (ECM) synthesis & secretion, regulation of autophagy, and antioxidant & anti-inflammation, etc. Natural compounds and extracts from TCMs are promising agents for the prevention and treatment of HF, and this review would be of great significance to development of novel drugs for treating HF.
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Affiliation(s)
- Wen-Qing Li
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wen-Hao Liu
- Department of Pharmacy, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Die Qian
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jia Liu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shi-Qiong Zhou
- Hospital of Nursing, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Lei Zhang
- Department of Vascular Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wei Peng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Li Su
- Institute of Translational Medicine, Shanghai University, Shanghai, China
| | - Hong Zhang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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14
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Thiruvengadam M, Chung IM, Samynathan R, Chandar SRH, Venkidasamy B, Sarkar T, Rebezov M, Gorelik O, Shariati MA, Simal-Gandara J. A comprehensive review of beetroot ( Beta vulgaris L.) bioactive components in the food and pharmaceutical industries. Crit Rev Food Sci Nutr 2022; 64:708-739. [PMID: 35972148 DOI: 10.1080/10408398.2022.2108367] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Beetroot is rich in various bioactive phytochemicals, which are beneficial for human health and exert protective effects against several disease conditions like cancer, atherosclerosis, etc. Beetroot has various therapeutic applications, including antioxidant, antibacterial, antiviral, and analgesic functions. Besides the pharmacological effects, food industries are trying to preserve beetroots or their phytochemicals using various food preservation methods, including drying and freezing, to preserve their antioxidant capacity. Beetroot is a functional food due to valuable active components such as minerals, amino acids, phenolic acid, flavonoid, betaxanthin, and betacyanin. Due to its stability, nontoxic and non-carcinogenic and nonpoisonous capabilities, beetroot has been used as an additive or preservative in food processing. Beetroot and its bioactive compounds are well reported to possess antioxidant, anti-inflammatory, antiapoptotic, antimicrobial, antiviral, etc. In this review, we provided updated details on (i) food processing, preservation and colorant methods using beetroot and its phytochemicals, (ii) synthesis and development of several nanoparticles using beetroot and its bioactive compounds against various diseases, (iii) the role of beetroot and its phytochemicals under disease conditions with molecular mechanisms. We have also discussed the role of other phytochemicals in beetroot and their health benefits. Recent technologies in food processing are also updated. We also addressed on molecular docking-assisted biological activity and screening for bioactive chemicals. Additionally, the role of betalain from different sources and its therapeutic effects have been listed. To the best of our knowledge, little or no work has been carried out on the impact of beetroot and its nanoformulation strategies for phytocompounds on antimicrobial, antiviral effects, etc. Moreover, epigenetic alterations caused by phytocompounds of beetroot under several diseases were not reported much. Thus, extensive research must be carried out to understand the molecular effects of beetroot in the near future.
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Affiliation(s)
- Muthu Thiruvengadam
- Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul, Republic of Korea
| | - Ill-Min Chung
- Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul, Republic of Korea
| | | | | | - Baskar Venkidasamy
- Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India
| | - Tanmay Sarkar
- Department of Food Processing Technology, Malda Polytechnic, West Bengal State Council of Technical Education, Government of West Bengal, Malda, India
| | - Maksim Rebezov
- Department of Scientific Advisers, V. M. Gorbatov Federal Research Center for Food Systems, Moscow, Russian Federation
- Department of Scientific Research, K.G. Razumovsky Moscow State University of Technologies and management (The First Cossack University), Moscow, Russia Federation
| | - Olga Gorelik
- Faculty of Biotechnology and Food Engineering, Ural State Agrarian University, Yekaterinburg, Russian Federation
- Ural Federal Agrarian Research Center of the Ural Branch, Russian Academy of Sciences, Yekaterinburg, Russian Federation
| | - Mohammad Ali Shariati
- Department of Scientific Research, K.G. Razumovsky Moscow State University of Technologies and management (The First Cossack University), Moscow, Russia Federation
| | - Jesus Simal-Gandara
- Universidade de Vigo, Nutrition and Bromatology Group, Analytical Chemistry and Food Science Department, Faculty of Science, Ourense, Spain
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15
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Early Metabolomic Markers of Acute Low-Dose Exposure to Uranium in Rats. Metabolites 2022; 12:metabo12050421. [PMID: 35629925 PMCID: PMC9147032 DOI: 10.3390/metabo12050421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 05/03/2022] [Accepted: 05/04/2022] [Indexed: 01/25/2023] Open
Abstract
Changes in metabolomics over time were studied in rats to identify early biomarkers and highlight the main metabolic pathways that are significantly altered in the period immediately following acute low-dose uranium exposure. A dose response relationship study was established from urine and plasma samples collected periodically over 9 months after the exposure of young adult male rats to uranyl nitrate. LC-MS and biostatistical analysis were used to identify early discriminant metabolites. As expected, low doses of uranium lead to time-based non-toxic biological effects, which can be used to identify early and delayed markers of exposure in both urine and plasma samples. A combination of surrogate markers for uranium exposure was validated from the most discriminant early markers for making effective predictions. N-methyl-nicotinamide, kynurenic acid, serotonin, tryptophan, tryptamine, and indole acetic acid associated with the nicotinate–nicotinamide and tryptophan pathway seem to be one of the main biological targets, as shown previously for chronic contaminations and completed, among others, by betaine metabolism. This study can be considered as a proof of concept for the relevance of metabolomics in the field of low-dose internal contamination by uranium, for the development of predictive diagnostic tests usable for radiotoxicological monitoring.
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16
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El Okle OS, Tohamy HG, Althobaiti SA, Soliman MM, Ghamry HI, Farrag F, Shukry M. Ornipural® Mitigates Malathion-Induced Hepato-Renal Damage in Rats via Amelioration of Oxidative Stress Biomarkers, Restoration of Antioxidant Activity, and Attenuation of Inflammatory Response. Antioxidants (Basel) 2022; 11:antiox11040757. [PMID: 35453442 PMCID: PMC9031224 DOI: 10.3390/antiox11040757] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 02/01/2023] Open
Abstract
The current study was instigated by investigating the ameliorative potential of Ornipural® solution against the hepato-renal toxicity of malathion. A total number of 35 male Wistar albino rats were divided equally into five groups. Group 1 served as control and received normal saline intraperitoneally. Group 2, the sham group, were administered only corn oil (vehicle of malathion) orally. Group 3 was orally intoxicated by malathion in corn oil at a dose of 135 mg/kg BW via intra-gastric gavage. Group 4 received malathion orally concomitantly with Ornipural® intraperitoneally. Group 5 was given Ornipural® solution in saline via intraperitoneal injection at a dose of (1 mL/kg BW). Animals received the treatment regime for 30 days. Histopathological examination revealed the harmful effect of malathion on hepatic and renal tissue. The results showed that malathion induced a significant decrease in body weight and marked elevation in the activity of liver enzymes, LDH, and ACP. In contrast, the activity of AchE and Paraoxonase was markedly decreased. Moreover, there was a significant increase in the serum content of bilirubin, cholesterol, and kidney injury markers. A significant elevation in malondialdehyde, nitric oxide (nitrite), and 8-hydroxy-2-deoxyguanosine was observed, along with a substantial reduction in antioxidant activity. Furthermore, malathion increased tumor necrosis factor-alpha, the upregulation of IL-1B, BAX, and IFN-β genes, and the downregulation of Nrf2, Bcl2, and HO-1 genes. Concurrent administration of Ornipural® with malathion attenuated the detrimental impact of malathion through ameliorating metabolic biomarkers, restoring antioxidant activity, reducing the inflammatory response, and improving pathologic microscopic alterations. It could be concluded that Ornipural® solution demonstrates hepatorenal defensive impacts against malathion toxicity at biochemical, antioxidants, molecular, and cellular levels.
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Affiliation(s)
- Osama S. El Okle
- Departement of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Alexandria University, Alexandria 22758, Egypt;
| | - Hossam G. Tohamy
- Departement of Pathology, Faculty of Veterinary Medicine, Alexandria University, Alexandria 22758, Egypt;
| | - Saed A. Althobaiti
- Biology Department, Turabah University College, Taif University, Taif 21995, Saudi Arabia;
| | - Mohamed Mohamed Soliman
- Clinical Laboratory Sciences Department, Turabah University College, Taif University, Taif 21995, Saudi Arabia;
| | - Heba I. Ghamry
- Department of Home Economics, College of Home Economics, King Khalid University, P.O. Box 960, Abha 61421, Saudi Arabia;
| | - Foad Farrag
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt;
| | - Mustafa Shukry
- Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt
- Correspondence:
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17
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Pannkuk EL, Laiakis EC, Angdisen J, Jayatilake MM, Ake P, Lin LYT, Li HH, Fornace AJ. Small Molecule Signatures of Mice Lacking T-cell p38 Alternate Activation, a Model for Immunosuppression Conditions, after Total-Body Irradiation. Radiat Res 2022; 197:613-625. [PMID: 35245386 DOI: 10.1667/rade-21-00199.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 01/24/2022] [Indexed: 11/03/2022]
Abstract
Several diagnostic biodosimetry tools have been in development that may aid in radiological/nuclear emergency responses. Of these, correlating changes in non-invasive biofluid small-molecule signatures to tissue damage from ionizing radiation exposure show promise for inclusion in predictive biodosimetry models. Integral to dose reconstruction has been determining how genotypic variation in the general population will affect model performance. Here, we used a mouse model that lacks the T-cell receptor specific alternative p38 pathway [p38αβY323F, double knock-in (DKI) mice] to determine how attenuated autoimmune and inflammatory responses may affect dose reconstruction. We exposed adult male DKI mice (8-10 weeks old) to 2 and 7 Gy in parallel with wild-type mice and assessed perturbations in urine (days 1, 3, 7) and serum (day 1) using a global metabolomics approach. A multidimensional scaling plot showed excellent separation of radiation-exposed groups in wild-type mice with slightly dampened responses in DKI mice. Validated metabolite panels were developed for urine [N6,N6,N6-trimethyllysine (TML), N1-acetylspermidine, spermidine, carnitine, acylcarnitine C21H35NO5, 4-aminohippuric acid] and serum [phenylalanine, glutamine, propionylcarnitine, lysophosphatidylcholine (LysoPC 14:0), LysoPC (22:5)] to determine the area under the receiver operating characteristic curve (AUROC). For both urine and serum, excellent sensitivity and specificity (AUROC > 0.90) was observed for 0 Gy vs. 7 Gy groups irrespective of genotype using identical metabolite panels. Similarly, excellent to fair classification (AUROC > 0.75) was observed for ≤2 Gy vs. 7 Gy mice for both genotypes, however, model performance declined (AUROC < 0.75) between genotypes after irradiation. Overall, these results suggest immunosuppression should not compromise small molecule multiplex panels used in dose reconstruction for biodosimetry.
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Affiliation(s)
- Evan L Pannkuk
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.,Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC
| | - Evagelia C Laiakis
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.,Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC
| | - Jerry Angdisen
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
| | - Meth M Jayatilake
- Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC
| | - Pelagie Ake
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
| | - Lorreta Yun-Tien Lin
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
| | - Heng-Hong Li
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.,Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC
| | - Albert J Fornace
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.,Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC
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18
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Baran M, Yay A, Onder GO, Canturk Tan F, Yalcin B, Balcioglu E, Yıldız OG. Hepatotoxicity and renal toxicity induced by radiation and the protective effect of quercetin in male albino rats. Int J Radiat Biol 2022; 98:1473-1483. [PMID: 35171756 DOI: 10.1080/09553002.2022.2033339] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
PURPOSE Although radiation is one of the basic methods commonly used in cancer treatment, it inevitably enters the field of treatment in healthy tissues and is adversely affected by the acute and chronic side effects of radiation. This study evaluated the possible protective effects of quercetin, an antioxidant agent, against liver and kidney damage in rats exposed to a whole-body single dose of radiation (10 Gy of gamma-ray). MATERIALS AND METHODS The study groups were formed as control, sham, quercetin, radiation, quercetin + radiation and radiation + quercetin using 60 male Wistar albino (200-250 g, 3 months old) rats, including 10 rats in each group. The gamma-ray provided by the Co60 teletherapy machine was given to the whole body as external irradiation. According to the groups, quercetin was administered to rats at 50 mg/kg/day via oral gavage before or after radiation administration. The rats were sacrificed the day after irradiation and the extracted tissue samples from all groups were compared histologically and immunohistochemically. DNA damage was determined by the neutral comet assay technique. Also, malondialdehyde (MDA) and glutathione peroxidase (GSH) were evaluated in liver and kidney tissues by the ELISA method. RESULTS Histopathological changes were observed altered morphology of liver and kidney tissues in the radiation groups. Sinusoidal dilatations, vacuolization, and hepatic parenchyma necrosis in the liver, while in kidneys, glomerular shrinkage, widened Bowman's space, tubular dilatation, and inflammation were evident. TNF-α, IL1-α, HIF1-α, and caspase 3 immunoreactivities in tissues were determined by immunohistochemistry. High caspase 3 positive cell number confirmed apoptosis, the comet parameters were decreased in the quercetin + radiation group. When compared to the control group, the exposure to radiation showed a marked elevation in MDA which was accompanied by high GSH. This damage was reduced in the quercetin + radiation group. CONCLUSIONS With the results obtained from the study; Quercetin is thought to have a protective potential against radiation-induced liver and kidney damage due to its radioprotective effect.
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Affiliation(s)
- Munevver Baran
- Department of Pharmaceutical Basic Science, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey
| | - Arzu Yay
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, Kayseri, Turkey.,Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Turkey
| | - Gozde Ozge Onder
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, Kayseri, Turkey
| | - Fazile Canturk Tan
- Department of Biophysics, Erciyes University, Faculty of Medicine, Kayseri, Turkey
| | - Betul Yalcin
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, Kayseri, Turkey
| | - Esra Balcioglu
- Department of Histology and Embryology, Erciyes University, Faculty of Medicine, Kayseri, Turkey.,Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Turkey
| | - Oguz Galip Yıldız
- Department of Radiation Oncology, Erciyes University, Faculty of Medicine, Kayseri, Turkey
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19
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Li Q, Qu M, Wang N, Wang L, Fan G, Yang C. Betaine Ameliorates Brain Damage in a Rat Model of Ischemia/Reperfusion Injury. J Neurophysiol 2022; 127:444-451. [PMID: 35020521 DOI: 10.1152/jn.00400.2021] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Brain ischemia and reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke, which could be alleviated by anti-oxidants with diminished oxidative stress. Betaine is a natural nutrient found in beetroot and seafood to improve cognitive performance in the elderly. The present study investigated whether betaine could protect the brain from I/R injury. Results showed that betaine treatment could reduce H2O2-induced cell death in the PC12 cell line. Pretreatment with betaine reduced the brain infarct volume and neuronal apoptosis in a rat I/R injury model induced by two-hour middle cerebral artery occlusion (MCAO). Biochemical analyses indicated that betaine treatment decreased pro-inflammatory cytokine production and reduced oxidative stress after I/R injury. Betaine increased the expression of anti-oxidative enzymes, such as glutathione peroxidase 4 (Gpx4) and superoxide dismutase 1 (Sod1), and anti-oxidative non-enzymatic genes, such as 3-mercaptopyruvate sulfurtransferase (Mpst), methionine sulfoxide reductases b1 (Msrb1), and Msrb2. These data suggest that betaine exerts a neuroprotective effect in I/R injury through enzymatic and non-enzymatic anti-oxidative systems and anti-inflammatory mechanisms.
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Affiliation(s)
- Qian Li
- Department of Neurology, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Mingwei Qu
- Department of Neurology, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Ningning Wang
- Department of Neurology, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Limin Wang
- Department of Neurology, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Guimei Fan
- Department of Neurology, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Chaoping Yang
- Department of Neurology, Cangzhou Central Hospital, Cangzhou, Hebei, China
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20
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Wang C, Ma C, Gong L, Dai S, Li Y. Preventive and therapeutic role of betaine in liver disease: A review on molecular mechanisms. Eur J Pharmacol 2021; 912:174604. [PMID: 34743980 DOI: 10.1016/j.ejphar.2021.174604] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 09/29/2021] [Accepted: 10/26/2021] [Indexed: 12/12/2022]
Abstract
Betaine is a kind of water-soluble quaternary amine-type alkaloid widely existing in food, such as wheat germ, beet, spinach, shrimp and wolfberry. As an important methyl donor and osmotic pressure regulator in human body, betaine plays an important role in a variety of physiological activities. In recent years, a large number of literatures have shown that betaine has good preventive and therapeutic effects on many liver diseases, including chemical or drug-induced liver injury, nonalcoholic fatty liver disease, alcoholic fatty liver disease, liver fibrosis, hepatitis B and hepatitis C. Therefore, by searching the databases of Web of Science, PubMed, SciFinder and CNKI, this paper has summarized the molecular mechanisms of betaine in improving liver diseases. The results show that the improvement of liver diseases by betaine is closely related to a variety of molecular mechanisms, including inhibition of inflammatory response, improvement of insulin resistance, reduction of endoplasmic reticulum stress, alleviation of liver oxidative stress, increase of autophagy, remodeling of intestinal flora and regulation of epigenetic modification. More importantly, nuclear transcription factor kappa (NF-κB), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α/γ (PPAR-α/γ), liver X receptor α (LXRα), protein kinase B (Akt), toll-like receptor 4 (TLR4) and cysteinyl aspartate specific proteinase-3 (Caspase-3) signaling pathways are considered as important molecular targets for betaine to improve liver diseases. These important findings will provide a direction and basis for further exploring the pathogenesis of various liver diseases and tapping the potential of betaine in the clinical treatment.
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Affiliation(s)
- Cheng Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Cheng Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Lihong Gong
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Shu Dai
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Yunxia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
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21
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Chen L, Zhu Y, Hu Z, Wu S, Jin C. Beetroot as a functional food with huge health benefits: Antioxidant, antitumor, physical function, and chronic metabolomics activity. Food Sci Nutr 2021; 9:6406-6420. [PMID: 34760270 PMCID: PMC8565237 DOI: 10.1002/fsn3.2577] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 08/06/2021] [Accepted: 08/19/2021] [Indexed: 12/19/2022] Open
Abstract
Previously, beetroot is mainly consumed as a food additive. In recent years, the beetroot, especially the betalains (betanin) and nitrates it contains, now has received increasing attention for their effective biological activity. Betalains have been proven to eliminate oxidative and nitrative stress by scavenging DPPH, preventing DNA damage, and reducing LDL. It also has been found to exert antitumor activity by inhibiting cell proliferation, angiogenesis, inducing cell apoptosis, and autophagy. In some chronic diseases, nitrate is the main component for lowing blood lipids, glucose, and pressure, while its role in treating hypertension and hyperglycemia has not been clearly stated. Moreover, the intake of nitrate-rich beetroot could enhance athletic performance and attenuate muscle soreness in certain types of exercise. The objective of this review is to provide sufficient evidence for the clarification of health benefits of beetroot, especially in the aspect of biooxidation, neoplastic diseases, some chronic diseases, and energy supplementation.
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Affiliation(s)
- Liping Chen
- Department of PharmacySchool of MedicineSir Run Run Shaw HospitalZhejiang UniversityHangzhouChina
| | - Yuankang Zhu
- College of Second Clinical MedicalWenzhou Medical UniversityWenzhouChina
| | - Zijing Hu
- Chemical Biology Research CenterCollege of Pharmaceutical SciencesWenzhou Medical UniversityWenzhouChina
| | - Shengjie Wu
- Department of PharmacySchool of MedicineSir Run Run Shaw HospitalZhejiang UniversityHangzhouChina
| | - Chengtao Jin
- Department of PharmacySchool of MedicineSir Run Run Shaw HospitalZhejiang UniversityHangzhouChina
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22
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Zhu W, Zhang X, Yu M, Lin B, Yu C. Radiation-induced liver injury and hepatocyte senescence. Cell Death Discov 2021; 7:244. [PMID: 34531376 PMCID: PMC8446062 DOI: 10.1038/s41420-021-00634-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 08/06/2021] [Accepted: 08/26/2021] [Indexed: 12/14/2022] Open
Abstract
Radiation-induced liver injury (RILI) is a major complication of radiotherapy during treatment for liver cancer and other upper abdominal malignant tumors that has poor pharmacological therapeutic options. A series of pathological changes can be induced by radiation. However, the underlying mechanism of RILI remains unclear. Radiation can induce cell damage via direct energy deposition or reactive free radical generation. Cellular senescence can be observed due to the DNA damage response (DDR) caused by radiation. The senescence-associated secretory phenotype (SASP) secreted from senescent cells can cause chronic inflammation and aggravate liver dysfunction for a long time. Oxidative stress further activates the signaling pathway of the inflammatory response and affects cellular metabolism. miRNAs clearly have differential expression after radiation treatment and take part in RILI development. This review aims to systematically profile the overall mechanism of RILI and the effects of radiation on hepatocyte senescence, laying foundations for the development of new therapies.
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Affiliation(s)
- Wei Zhu
- Department of Gastroenterology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaofen Zhang
- Department of Gastroenterology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Mengli Yu
- Department of Gastroenterology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Bingru Lin
- Department of Gastroenterology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
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23
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Ma X, Jiang Y, Wen J, Zhao Y, Zeng J, Guo Y. A comprehensive review of natural products to fight liver fibrosis: Alkaloids, terpenoids, glycosides, coumarins and other compounds. Eur J Pharmacol 2020; 888:173578. [PMID: 32976828 DOI: 10.1016/j.ejphar.2020.173578] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 09/14/2020] [Accepted: 09/15/2020] [Indexed: 02/07/2023]
Abstract
The discovery of drugs to treat liver fibrosis has long been a challenge over the past decades due to its complicated pathogenesis. As a primary approach for drug development, natural products account for 30% of clinical drugs used for disease treatment. Therefore, natural products are increasingly important for their medicinal value in liver fibrosis therapy. In this part of the review, special focus is placed on the effect and mechanism of natural compounds, including alkaloids, terpenoids, glycosides, coumarins and others. A total of 36 kinds of natural compounds demonstrate significant antifibrotic effects in various liver fibrosis models in vivo and in hepatic stellate cells (HSCs) in vitro. Revealing the mechanism will provide further basis for clinical conversion, as well as accelerate drug discovery. The mechanism was further summarized with the finding of network regulation by several natural products, such as oxymatrine, paeoniflorin, ginsenoside Rg1 and taurine. Moreover, there are still improvements needed in investigating clinical efficacy, determining mechanisms, and combining applications, as well as semisynthesis and modification. Therefore, natural products area promising resource for agents that protect against liver fibrosis.
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Affiliation(s)
- Xiao Ma
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Yinxiao Jiang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Jianxia Wen
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Department of Pharmacy, Fifth Medical Center of PLA General Hospital, Beijing, 100039, China
| | - Yanling Zhao
- Department of Pharmacy, Fifth Medical Center of PLA General Hospital, Beijing, 100039, China.
| | - Jinhao Zeng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
| | - Yaoguang Guo
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
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24
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Role of Diosmin in protection against the oxidative stress induced damage by gamma-radiation in Wistar albino rats. Regul Toxicol Pharmacol 2020; 113:104622. [DOI: 10.1016/j.yrtph.2020.104622] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 01/02/2020] [Accepted: 02/18/2020] [Indexed: 01/04/2023]
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25
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Borzoueisileh S, Shabestani Monfared A, Ghorbani H, Mortazavi SMJ, Zabihi E, Pouramir M, Doustimotlagh AH, Shafiee M, Niksirat F. Assessment of function, histopathological changes, and oxidative stress in liver tissue due to ionizing and non-ionizing radiations. CASPIAN JOURNAL OF INTERNAL MEDICINE 2020; 11:315-323. [PMID: 32874440 PMCID: PMC7442457 DOI: 10.22088/cjim.11.3.315] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Compared to past decades, humans are exposed to rapidly increasing levels of radiofrequency electromagnetic radiations (RF-EMF). Despite numerous studies, the biological effects of human exposure to different levels of RF-EMF are not fully understood yet. This study aimed to evaluate the bioeffects of exposure to "900/1800 MHz" and "2.4 GHz" RF-EMFs, and x-rays alone as well as their potential interactions, i.e. inducing simple additive, adaptive, or synergistic effects. METHODS 120 Wistar rats were randomly divided into ten groups of 12 each. The rats were exposed to RF-EMF, 10 cGy, and 8 Gy x-rays, a combination of these exposures, or only sham-exposed. The levels of liver enzymes were determined in serum samples by an auto-analyzer. Moreover, the histopathological changes, and the levels of malondialdehyde (MDA), nitric oxide, ferric reducing antioxidant power, total thiols, and protein carbonyl (PCO) were measured. RESULTS Among the markers of liver function, gamma-glutamyltransferase was not associated with irradiation but, aspartate transaminase, alanine transaminase, and alkaline phosphatase showed some levels of association. MDA and PCO levels after 8 Gy irradiation increased, but pre-exposure to RF-EMF could modulate their changes. At the cellular level, the frequency of lobular inflammation was associated with the type of intervention. CONCLUSION The exposure to both ionizing and non-ionizing radiations could alter some liver function tests. A short term pre-exposure to RF-EMF before exposure to an 8 Gy challenging dose of x-rays caused the alterations in oxidative stress markers and liver function tests, which indicate that oxidative stress is possibly involved in the adaptive response.
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Affiliation(s)
- Sajad Borzoueisileh
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Ali Shabestani Monfared
- Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol Iran
| | - Hossein Ghorbani
- Pathology Department, Babol University of Medical Sciences, Babol, Iran
| | - S M J Mortazavi
- Department of Medical Physics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ebrahim Zabihi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Mehdi Pouramir
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | | | - Mohsen Shafiee
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Fatemeh Niksirat
- Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol Iran
- Department of Medical Physics Radiobiology and Radiation Protection, School of Medicine, Babol University of Medical Sciences, Babol, Iran
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26
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Albasher G, Albrahim T, Alsultan N, Alfaraj S, Alharthi MS, Kassab RB, Abdel Moneim AE. Red beetroot extract mitigates chlorpyrifos-induced reprotoxicity associated with oxidative stress, inflammation, and apoptosis in rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:3979-3991. [PMID: 31823260 DOI: 10.1007/s11356-019-07009-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 11/11/2019] [Indexed: 06/10/2023]
Abstract
The goal of our investigation is to evaluate the potential protective efficacy of red beetroot extract (RBR) against testicular toxicity produced by CPF in rats. CPF exposure decreased the weight of testis and the levels of luteinizing hormone, follicle stimulating hormone and testosterone. CPF impaired also the oxidative status in favor of pro-oxidant molecules in the testicular tissue. Additionally, CPF stimulated the production of pro-inflammatory cytokines and their gene expression. Concomitantly, an apoptotic cascade has been observed upon CPF intoxication. However, RBR administration protected the testis tissue through modulating the hormonal level, inhibiting the oxidative damage, inflammation and the apoptotic responses following CPF intoxication. The obtained data recommend the use of RBR to prevent CPF-induced testicular damage via antioxidant, anti-inflammatory, and anti-apoptotic pathways.
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Affiliation(s)
- Gadah Albasher
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
| | - Tarfa Albrahim
- Department of Health Sciences, Clinical Nutrition, College of Health and Rehabilitation Sciences, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Nouf Alsultan
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Saleh Alfaraj
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Mada S Alharthi
- Medical Laboratory Science Microbiology, College of Applied Medical Sciences, Shaqra University, Shaqra, Saudi Arabia
| | - Rami B Kassab
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt
| | - Ahmed E Abdel Moneim
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt
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27
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Singh VK, Seed TM. Pharmacological management of ionizing radiation injuries: current and prospective agents and targeted organ systems. Expert Opin Pharmacother 2020; 21:317-337. [PMID: 31928256 PMCID: PMC6982586 DOI: 10.1080/14656566.2019.1702968] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 12/06/2019] [Indexed: 12/20/2022]
Abstract
Introduction: There is a limited array of currently available medicinals that are useful for either the prevention, mitigation or treatment of bodily injuries arising from ionizing radiation exposure.Area covered: In this brief article, the authors review those pharmacologic agents that either are currently being used to counter the injurious effects of radiation exposure, or those that show promise and are currently under development.Expert opinion: Although significant, but limited progress has been made in the development and fielding of safe and effective pharmacotherapeutics for select types of acute radiation-associated injuries, additional effort is needed to broaden the scope of drug development so that overall health risks associated with both short- and long-term injuries in various organ systems can be reduced and effectively managed. There are several promising radiation countermeasures that may gain regulatory approval from the government in the near future for use in clinical settings and in the aftermath of nuclear/radiological exposure contingencies.
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Affiliation(s)
- Vijay K. Singh
- Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
- Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
| | - Thomas M Seed
- Tech Micro Services, 4417 Maple Avenue, Bethesda, MD 20814, USA
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28
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Abdel-Magied N, Elkady AA. Possible curative role of curcumin and silymarin against nephrotoxicity induced by gamma-rays in rats. Exp Mol Pathol 2019; 111:104299. [PMID: 31442446 DOI: 10.1016/j.yexmp.2019.104299] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 08/05/2019] [Accepted: 08/20/2019] [Indexed: 12/22/2022]
Abstract
Curcumin (CUR) and silymarin (SLM) are powerful antioxidant and anti-inflammatory compounds with beneficial protective effects against renal diseases. The purpose of this study was to evaluate the efficacy of CUR and SLM alone or in combination on radiation (IR) induced kidney injury. The results showed that CUR and SLM alone or in combination attenuated the oxidative stress denoted by a reduction in the level of malondialdehyde (MDA), hydrogen peroxide (H2O2) and advanced oxidation protein products (AOPP) along with a marked increase of glutathione GSH content and total antioxidant capacity (TAC). Additionally, a significant decrease in the level of blood urea nitrogen (BUN), creatinine, Cystatin-C (CYT-C), neutrophil gelatinase-associated lipocalin (N-GAL) and Kidney Injury Molecule-1 (Kim-1) was recorded. Moreover, the treatment resulted in a remarkable decline in the serum levels of interleukin-18(IL-18), tumor necrosis factor- alpha (TNF-α), C reactive protein (CRP), BCL2 associated X protein (Bax), Factor-related Apoptosis (FAS) and the activity of Caspase-3 associated by an increase of B-cell CLL/lymphoma 2 (Bcl2) level. The results were confirmed with the histopathological examination. Kidney of irradiated showed glomerular atrophy, massive necrotic changes of expanded tubules with hyaline cast inside some tubules and apoptotic changes were recorded in some renal tubules. While irradiated rats treated with CUR and SLM exhibited marked preservation of the cellular structure of their kidney tissue. In conclusion, the combination of CUR and SLM could be more potent than a single agent on the biochemical and histological changes of the irradiated rat renal tissue.
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Affiliation(s)
- Nadia Abdel-Magied
- Radiation Biology Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), P.O. Box 29, Nasr City, Cairo, Egypt.
| | - Ahmed A Elkady
- Health Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), P.O. Box 29, Nasr City, Cairo, Egypt.
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29
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Abdel-Magied N, Shedid SM. The effect of naringenin on the role of nuclear factor (erythroid-derived 2)-like2 (Nrf2) and haem oxygenase 1 (HO-1) in reducing the risk of oxidative stress-related radiotoxicity in the spleen of rats. ENVIRONMENTAL TOXICOLOGY 2019; 34:788-795. [PMID: 30843661 DOI: 10.1002/tox.22745] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 02/18/2019] [Accepted: 02/23/2019] [Indexed: 06/09/2023]
Abstract
The present study was to evaluate the radiomitigative effect of naringenin (NRG) on the modulation of ionizing radiation (IR)-induced spleen injury. Rats were exposed to 12 Gy (3Gy/two times/week). NRG (50mg/Kg), was orally given one hour after the first radiation dose, and daily continued during the irradiation period. Rats were sacrificed 1 day after the last dose of radiation. NRG showed a significant decrease of malondialdehyde, hydrogen peroxide with a significant elevation of superoxide dismutase, catalase and glutathione peroxidase activities and glutathione content. Moreover, NRG confirmed the intracellular defense mechanisms through activation of nuclear factor (erythroid-derived 2)-like2 (Nrf2) and haem oxygenase-1 (HO-1) levels and their protein expression. In addition, NRG deactivated the nuclear factor-κB (NF-κB) and reduced the pro-inflammatory cytokines. Further, NRG showed positive modulation in the haematological values (WBCs, RBCs, Hb, Hct% and PLt). In conclusion, these results suggested that NRG reversed the IR-induced redox-imbalance in the rat spleen.
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Affiliation(s)
- Nadia Abdel-Magied
- Radiation Biology Research Department, National Centre for Radiation Research and Technology (NCRRT), Atomic Energy Authority (AEA), Cairo, Egypt
| | - Shereen M Shedid
- Radiation Biology Research Department, National Centre for Radiation Research and Technology (NCRRT), Atomic Energy Authority (AEA), Cairo, Egypt
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30
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Huang F, Chen X, Jiang X, Niu J, Cui C, Chen Z, Sun J. Betaine ameliorates prenatal valproic-acid-induced autism-like behavioral abnormalities in mice by promoting homocysteine metabolism. Psychiatry Clin Neurosci 2019; 73:317-322. [PMID: 30821067 DOI: 10.1111/pcn.12833] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 02/08/2019] [Accepted: 02/25/2019] [Indexed: 12/15/2022]
Abstract
AIM Abnormally high levels of homocysteine (Hcy) are associated with autism spectrum disorder. Betaine is a methyl group donor in Hcy metabolism, and is known to prevent noxious Hcy accumulation. This study explored whether betaine could influence Hcy metabolism in a mouse model of autism and ameliorate behavioral abnormalities. METHODS Pregnant ICR mice were administered valproic acid (VPA) intraperitoneally on Embryonic Day 12.5. Serum Hcy concentrations in the offspring were measured by enzyme-linked immunosorbent assay. Expressions of Hcy-metabolism-related enzymes, betaine-Hcy methyltransferase, cystathionine β-synthase, and methionine synthase, were measured by quantitative reverse transcription polymerase chain reaction and western blotting. Offspring were treated by either betaine or saline at the age of 8 weeks and serum Hcy concentrations were measured. Social behaviors were assessed by sniff-duration test and three-chamber test. Repetitive behavior was evaluated by marble-burying test. Tail-flick test was performed to measure nociceptive sensitivity. RESULTS Prenatal VPA-exposed mice showed significantly elevated Hcy concentrations and decreased betaine-Hcy methyltransferase expression. Treatment with betaine could reduce Hcy level in VPA-exposed mice, attenuate social impairment and repetitive behavior, and normalize nociceptive sensitivity in this model. CONCLUSION Betaine could ameliorate autism-like features and play a beneficial role in a mouse autism model induced by prenatal VPA exposure.
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Affiliation(s)
- Fei Huang
- Psychiatric Ward, Qingdao Mental Health Center, Qingdao, China
| | - Xiaoqin Chen
- Psychiatric Ward, Qingdao Mental Health Center, Qingdao, China
| | - Xiangzhi Jiang
- Psychiatric Ward, Qingdao Mental Health Center, Qingdao, China
| | - Juan Niu
- Psychological Clinic, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Cuicui Cui
- Psychosomatic Ward, Shandong Mental Health Center, Jinan, China
| | - Zhenli Chen
- Psychosomatic Ward, Shandong Mental Health Center, Jinan, China
| | - Jun Sun
- Psychiatric Ward, Qingdao Mental Health Center, Qingdao, China
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