PROTECTIVE ROLE OF ESCULETIN ON ETHANOL AND LIPOPOLYSACCHARIDE-INDUCED HEPATOTOXICITY IN MALE WISTAR RATS

Alcohol-related liver diseases and their associated damage pose significant health concerns globally. Among potential remedies, esculetin, a saturated dicarboxylic acid known for its anti-inflammatory and antioxidant attributes, stands out. This study aims to explore the hepatoprotective effects of esculetin in rat models afflicted by liver damage induced by ethanol+ lipopolysaccharide (LPS). To emulate alcoholic liver damage, adult Wistar rats were subjected to 10 days of ethanol (5 mL/kg b.w) and a single dose of LPS (5 mL/kg b.w) orally on the 11^th day. Esculetin was administered orally to rats for the same 11 days duration, at doses of 50 mg/kg b.w, with a one-hour interval before inducer administration. The results revealed a remarkable reduction in the elevated levels of serum enzymes AST, ALT, ALP, and GGT following esculetin treatment, effectively restoring them to normal levels. Moreover, esculetin exhibited a substantial decrease in liver lipid peroxidation levels compared to the ethanol and ethanol+LPS group, indicating its potent management of severe oxidative stress. The addition of esculetin to the ethanol and ethanol+LPS exposed rats significantly elevates both enzymatic and non-enzymatic antioxidant activities in the liver tissue. Furthermore, when administered alongside ethanol+LPS, esculetin restored the significant alterations in liver lipid levels in the rats. Histopathological analyses provided further evidence of esculetin hepatoprotective qualities, as the treated groups exhibited a restoration of normal hepatocellular architecture, unlike the group that solely received ethanol and ethanol+LPS. This study concludes that esculetin effectively shields the liver from ethanol+LPS-induced toxicity, showcasing its potential to mitigate alcohol-related liver harm.