Alhusaini Ahlam, Alghilani Shahad, Alhuqbani Waad, Hasan Iman H
Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Dose Response. 2021 Apr 26;19(2):15593258211011360. doi: 10.1177/15593258211011360. eCollection 2021 Apr-Jun.
Mercury is one of the most harmful heavy metals and its toxicity causes severe multi-organ dysfunction. This study was designed to explore novel molecular pathways involved in the hepatoprotective effect of vitamin E (Vit-E) and (Lac-B) against mercury toxicity.
Acute hepatotoxicity was induced by administration of high dose of mercuric chloride (HgCl) in male rats, Vit-E or/and Lac-B were given along with HgCl for 2 weeks. The effects of those antioxidants were studied focusing on their anti-apoptotic, anti-oxidative stress and anti-inflammatory eficacies. Histopathological examinations were also conducted.
The administration of HgCl induced liver injury which manifested by elevation in serum ALT and AST. Liver MDA, caspase-3 and TNF-α levels were markedly increased; whereas, GSH level and SOD activity were declined. HgCl significantly elevated the expressions of hepatic CHOP, GPR87, NF-κB and mTOR. Histopathological examination revealed massive hepatocyte degeneration following HgCl administration. Treatment with Vit-E or/and Lac-B restored the normal levels of the previously mentioned parameters, as well as improved hepatic architecture.
Vit-E and Lac-B provided protective effect against HgCl-induced hepatotoxicity via reduction of oxidative stress and inflammation, and downregulation of CHOP, GPR87, NF-κB and mTOR proteins' expressions.
汞是最有害的重金属之一，其毒性会导致严重的多器官功能障碍。本研究旨在探索维生素E（Vit-E）和乳糖醇（Lac-B）对汞毒性的肝保护作用所涉及的新分子途径。
给雄性大鼠高剂量氯化汞（HgCl）诱导急性肝毒性，同时给予Vit-E或/和Lac-B与HgCl一起处理2周。重点研究这些抗氧化剂的抗凋亡、抗氧化应激和抗炎功效。还进行了组织病理学检查。
HgCl给药诱导肝损伤，表现为血清ALT和AST升高。肝脏丙二醛（MDA）、半胱天冬酶-3（caspase-3）和肿瘤坏死因子-α（TNF-α）水平显著升高；而谷胱甘肽（GSH）水平和超氧化物歧化酶（SOD）活性下降。HgCl显著提高肝脏CHOP、GPR87、核因子-κB（NF-κB）和哺乳动物雷帕霉素靶蛋白（mTOR）的表达。组织病理学检查显示HgCl给药后大量肝细胞变性。用Vit-E或/和Lac-B治疗可恢复上述参数的正常水平，并改善肝脏结构。
Vit-E和Lac-B通过减轻氧化应激和炎症以及下调CHOP、GPR87、NF-κB和mTOR蛋白的表达，对HgCl诱导的肝毒性提供保护作用。
