Feselol Ameliorates Acetaminophen‐Induced Hepatotoxicity Through Multi‐Pathway Modulation of Oxidative Stress, Inflammation, and Apoptosis in Mice

BACKGROUND AND AIM: Acetaminophen (APAP) overdose is a major cause of drug-related acute liver failure around the world. The limited treatment options beyond N-acetylcysteine (NAC) show a clear need for new liver-protective agents. Feselol, a natural compound known for its strong antioxidant effects, has become a potential candidate. This research aimed to evaluate feselol's anti-inflammatory, anti-apoptotic, and protective qualities against APAP-induced acute liver damage in a mouse model. MATERIAL AND METHOD: The experiment included 42 mice divided into 7 groups, with some being administered a toxic dose of APAP only and others being given APAP in combination with 25 or 50 mg/kg of feselol. Serum levels of AST (serum aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), and GGT (gamma-glutamyl transferase) were examined. SOD (superoxide dismutase), CAT (catalase), GPx (glutathione peroxidase) activities and MDA (malondialdehyde) levels were measured by colorimetric method. The liver tissue was analyzed through H&E staining. The expression of IL-1β, TNF-α, Bax, Caspase 3, and Bcl-2 genes was also examined by Real-time PCR. RESULTS: The results showed that treatment of feselol at different doses with APAP led to a decrease in MDA levels to 23.25 nmol/mg (p < 0.05). Also, the activities of SOD, CAT and GPx enzymes in the group treated with a dose of 50 mg/kg of feselol with APAP were 33.09, 109.86, and 109.80, respectively, which was significant compared to the APAP group (p < 0.05). The results showed that simultaneous treatment with feselol and APAP resulted in a decrease in IL-1β and TNF-α gene expression by 1.67 and 1.015 fold, respectively (p < 0.05). Also, the expression of Bax (3.22-fold) and Caspase 3 (1.26-fold) genes decreased in the feselol-treated group and the expression of Bcl-2 (0.59-fold) gene increased. In the group that received APAP and feselol, the liver tissue was close to that of the control group. Feselol (50 mg/kg) coadministered with APAP significantly reduced ALT, AST, ALP, and GGP enzyme activity compared to the APAP-treated group (p < 0.05). CONCLUSION: This study is notable for the discovery of feselol's pharmacological effects as a preventive drug against oxidative stress-associated hepatic impairment.