Hepatoprotective effect of diosmetin against thioacetamide-induced liver injury via modulating Bax/NF-κB/caspase-3/Nrf-2/PPAR signaling pathway in rats.

Thioacetamide (TAA), an established liver toxic chemical, is used to develop experimental models of liver injury by inducing inflammation, oxidative stress, and apoptosis. The current study investigates the hepatoprotective effect of diosmetin (DSM), a bioflavonoid molecule, with mechanistic investigations using an in vivo TAA-induced liver injury model because there is no precedence. In the current investigation, 30 Wistar rats were randomly assigned to five groups. The rats were given TAA (200 mg/kg) and DSM (50 and 100 mg/kg body weight) for 8 weeks. Liver function biomarkers (ALT, ASP, AST, bilirubin, GGT, CRP, albumin, globulin, and total protein) and inflammatory markers were analyzed on serum, whereas antioxidant levels, histological evaluation, and apoptotic markers were evaluated on liver tissue. The finding of this study indicated that DSM ameliorates TAA-induced increases in ALT, ASP, AST, bilirubin, GGT, CRP, MDA, albumin, globulin, total protein, and antioxidant enzyme activity such as SOD, CAT, and GSH levels. DSM reduced alterations in inflammatory biomarkers (IL-6, IL-1β, TNF-α) and apoptotic markers (Bax, NF-κB, caspase-3, Nrf-2, PPAR) in liver tissues. Furthermore, DSM therapy resulted in significant major changes in liver histology, fibrosis, and cell death. The current study's findings demonstrated that DSM significantly decreases hepatotoxicity by enhancing liver structure and function while suppressing oxidative stress, inflammation, and apoptosis.