Chronic hepatotoxicity is a debilitating and frequently life-threatening disease resulting in progressive liver failure. The toxic chemical, thioacetamide (TAA) is used to evaluate hepatoprotective agents, and the polyphenolic compound, resveratrol was proposed as a novel treatment for diseases with hyperactivation of the mammalian target of rapamycin (mTOR) cell signaling pathway. This analysis sought to investigate the potential protective effect of resveratrol against liver injury induced by TAA via the inhibition of hepatic mTOR. Model group rats received several injections of TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed at week 10 and the protective group was pretreated with resveratrol (20 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for biomarkers of inflammation and assessed the levels of mTOR protein in all animal groups. In addition, blood samples were assayed for biomarkers of liver injury enzyme. TAA substantially damaged the hepatic tissue of the model group such as infiltration of inflammatory cells, vacuolated cytoplasm, dark pyknotic nuclei, and dilated congested blood vessel that were effectively protected by resveratrol. Resveratrol also significantly (p<0.05) inhibited TAA-induced mTOR, high sensitivity c-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in harvested liver homogenates and blood samples. Thus, we conclude that resveratrol effectively protects against TAA-induced hepatotoxicity in rats, possibly due to the inhibition of mTOR and inflammation.
KEY WORDS: Liver injury; Thioacetamide; mTOR; Resveratrol; Inflammation; Rat model.