Apocynin ameliorates liver fibrosis events in vivo through modulation of oxidative stress, inflammatory, and apoptotic mediators

Abstract

The liver has a tremendous regeneration potential, yet chronic liver injury poses a life-threatening condition if not managed appropriately. Apocynin, an NADPH oxidase inhibitor, has been a central focus of attention in recent years due to its significant antioxidant/anti-inflammatory potentials. In this study, we evaluated the acute toxicity and hepatoprotective effects of Apocynin against thioacetamide (TAA)-induced liver fibrosis in rats. Liver fibrosis was induced by 200 mg/kg TAA three times/week for two months, along with treatment with distilled water (positive control), silymarin (reference, 50 mg/kg), or apocynin (50 and 100 mg/kg/day). Hepatic tissues were screened for histopathological, biochemical, and immunohistochemical changes, while hepatic homogenate was examined for the antioxidant contents (catalase, CAT; superoxide dismutase, SOD) and MDA levels. Apocynin treatment showed significant hepatoprotective effects against TAA-hepatotoxicity, evidenced by reduced hepatic tissue alterations with a slight fibroplasia, reduction of hepatomegaly, less hepatic nodules/necrosis, and recovered hepatic function. Additionally, apocynin administration reduced oxidative stress by lowering pro-oxidants (MDA) and up-regulating antioxidants (SOD and CAT). Furthermore, the anti-apoptotic and anti-fibrotic effects of apocynin were confirmed by reduced pro-apoptotic P53 proteins and β-catenin (tissue proliferation/aggregation enhancer). Apocynin treatment ameliorated ECM generation (lowered collagen bundles/fibrous septa) and reduced inflammatory (less TNf-α and IL-6 cytokines) mediators, all of which restored liver functional parameters (ALT, AST, ALP, and albumin). Apocynin attenuated TAA-mediated liver fibrosis by its modulatory potentials on several cytoprotective mechanisms associated with the oxidative stress/inflammation, making it a viable therapeutic source for liver fibrosis.

Keywords: Apocynin, Liver Fibrosis, Thioacetamide, Antioxidants, Histopathology