Biotechnology, Water, Environment and Health Laboratory, Faculty of Natural and Life Sciences, University Abbes Lagherour, Khenchela, Algeria.
Department of Molecular and Cellular Biology, Faculty of Natural and Life Sciences, University Abbes Lagherour, Khenchela, Algeria.
Sci Rep. 2024 Mar 6;14(1):5555. doi: 10.1038/s41598-024-55857-1.
Methionine (Met) rich diet inducing oxidative stress is reported to alter many organs. Proteasome as a regulator of oxidative stress can be targeted. This study was performed to investigate if excessive methionine supplementation causes hepatotoxicity related to proteasome dysfunction under endogenous oxidative stress in rats. Male Wistar albino rats (n = 16) were divided into controls and treated groups. The treated rats (n = 08) received orally L-methionine (1 g/kg/day) for 21 days. Total homocysteine (tHcy), total oxidant status (TOS), total antioxidant status (TAS), hepatic enzymes levels: aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), with total bilirubin (TBil), albumin (Alb), and C-reactive protein (CRP) were determined in plasma by biochemical assays. Liver supernatants were used for malondialdehyde (MDA), protein carbonyls (PC), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), 20S proteasome activities and their subunits expression, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) evaluation by appropriate methods and light microscopy for liver histological examination. Methionine treatment increased homocysteine, TOS, oxidative stress index (OSI), MDA and PC but decreased TAS, GSH, CAT, SOD, GPx with the 20S proteasome activities and their β subunits expression. Liver proteins: AST, ALT, LDH, ALP, TBil and CRP were increased but Alb was decreased. Liver histology was also altered. An increase in liver TNF-α and IL-6 levels were observed. These findings indicated that methionine supplementation associated oxidative stress and proteasome dysfunction, caused hepatotoxicity and inflammation in rat. Further investigations should be to better understand the relation between methionine, oxidative stress, proteasome, and liver injuries.
蛋氨酸（Met）丰富的饮食诱导氧化应激被报道会改变许多器官。蛋白酶体作为氧化应激的调节剂可以成为靶点。本研究旨在探讨过量蛋氨酸补充是否会在大鼠内源性氧化应激下引起与蛋白酶体功能障碍相关的肝毒性。雄性 Wistar 白化大鼠（n=16）分为对照组和治疗组。治疗组（n=08）每天口服 L-蛋氨酸（1 g/kg）21 天。通过生化分析测定血浆中总同型半胱氨酸（tHcy）、总氧化状态（TOS）、总抗氧化状态（TAS）、天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、乳酸脱氢酶（LDH）、碱性磷酸酶（ALP）、总胆红素（TBil）、白蛋白（Alb）和 C 反应蛋白（CRP）。用适当的方法和肝组织学检查的光镜评估肝上清液中的丙二醛（MDA）、蛋白羰基（PC）、谷胱甘肽（GSH）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）、20S 蛋白酶体活性及其β亚基表达、肿瘤坏死因子-α（TNF-α）和白细胞介素 6（IL-6）。蛋氨酸治疗增加了同型半胱氨酸、TOS、氧化应激指数（OSI）、MDA 和 PC，但降低了 TAS、GSH、CAT、SOD、GPx 以及 20S 蛋白酶体的活性和其β亚基的表达。肝蛋白：AST、ALT、LDH、ALP、TBil 和 CRP 增加，但 Alb 减少。肝组织学也发生了改变。还观察到肝 TNF-α和 IL-6 水平升高。这些发现表明，蛋氨酸补充与氧化应激和蛋白酶体功能障碍相关，导致大鼠肝毒性和炎症。进一步的研究应该更好地了解蛋氨酸、氧化应激、蛋白酶体和肝损伤之间的关系。
