Vitamin E and Lactobacillus Provide Protective Effects Against Liver Injury Induced by HgCl(2): Role of CHOP, GPR87, and mTOR Proteins

BACKGROUND AND OBJECTIVE: 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 Lactobacillius plantarum (Lac-B) against mercury toxicity. [Image: see text] METHOD: Acute hepatotoxicity was induced by administration of high dose of mercuric chloride (HgCl(2)) in male rats, Vit-E or/and Lac-B were given along with HgCl(2) 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. RESULTS: The administration of HgCl(2) 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(2) significantly elevated the expressions of hepatic CHOP, GPR87, NF-κB and mTOR. Histopathological examination revealed massive hepatocyte degeneration following HgCl(2) administration. Treatment with Vit-E or/and Lac-B restored the normal levels of the previously mentioned parameters, as well as improved hepatic architecture. CONCLUSION: Vit-E and Lac-B provided protective effect against HgCl(2)-induced hepatotoxicity via reduction of oxidative stress and inflammation, and downregulation of CHOP, GPR87, NF-κB and mTOR proteins’ expressions.