Apigenin role against thioacetamide-triggered liver fibrosis: Deciphering the PPARγ/TGF-β۱/NF-κB and the HIF/FAK/AKT pathways

Introduction: Liver tissue malfunction is a severe worldwide health concern that arises from various chronic liver conditions. The goal of this investigation was to look into the anti-fibrotic effect of apigenin (APG), an antioxidant found in various plants, versus thioacetamide (TAA)-triggered hepatic scarring in rats and the potential mechanisms behind it. Methods: TAA was administered thrice weekly (۱۰۰ mg/kg, i.p.) for two weeks to produce hepatic scarring. APG was administered after TAA for ۱۴ days (۵ or ۱۰ mg/kg, orally). Thereafter, hepatic liver enzymes, inflammatory markers, fibrotic indicators, and histopathological changes were evaluated. Results: TAA increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reduced albumin and total protein, elevated hepatic level of lipid peroxidation, focal adhesion kinase (FAK), hypoxia-inducible factor-۱α (HIF-۱α), and inflammatory cytokines, decreased interleukin-۱۰ (IL-۱۰), reduced hepatic expression of peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor-erythroid factor ۲-related factor ۲ (Nrf۲), and elevated serine-threonine protein kinase (AKT) expression. Furthermore, TAA increased hepatic contents of collagen I, connective tissue growth factor (CTGF), hydroxyproline, and alpha-smooth muscle actin. On the other hand, APG evaded these changes and mitigated the harmful effects of TAA in a dose-dependent way. Histopathological and immunohistochemical observations reinforced these biochemical outcomes. Conclusion: APG can potentially alleviate liver fibrosis mediated via FAK and HIF۱ inhibiting signaling pathways.

کلیدواژه ها:

Malondialdehyde ، Transforming growth factor beta ۱ ، Tumour necrosis factor alpha Alpha-smooth muscle actin ، Hydroxyproline ، Liver fibrosis ، Rats