UTTAR PRADESH JOURNAL OF ZOOLOGY

Ethanol-induced liver disease is a major global health concern. This study investigated the protective effects of esculetin against hepatotoxicity induced by ethanol and ethanol combined with lipopolysaccharide (LPS) in rats, with a focus on its anti-apoptotic and anti-inflammatory mechanisms. In this experiment, thirty adult male Wistar rats were randomly assigned to five groups (six rats per group). The rats received ethanol (5 mL/kg b.w) for 10 days, followed by a single intraperitoneal dose of LPS (5 mL/kg b.w) on the 11th day. Esculetin was administered orally at 50 mg/kg b.w for the same 11-day period, one hour before ethanol or LPS administration. At the end of the study, hepatotoxicity was assessed through biochemical, histopathological, immunohistochemical, and mRNA expression analyses. Biochemical evaluation revealed significant increases in bilirubin, creatinine, and phase II detoxification enzymes, along with reductions in phase I detoxification enzymes in the ethanol and ethanol+LPS groups. Additionally, ethanol and ethanol+LPS exposure upregulated the expression of Bax, caspase-3, TNF-α, NF-κB, and COX-2, while downregulating Bcl-2 expression. However, esculetin treatment mitigated these biochemical and molecular alterations, restoring them closer to normal levels compared to the ethanol and ethanol+LPS groups. These findings suggest that esculetin may serve as a potential therapeutic agent for ethanol-induced liver injury by exerting anti-apoptotic and anti-inflammatory effects. Further research using this model could provide valuable insights into the mechanisms underlying alcoholic liver disease in humans.