Hepato-Curative Effect of Cholecalciferol (Vitamin D) on Fipronil-Induced Liver Damage via Up-regulation of AMPK-α, and PPAR-γ Signaling Pathways in Male Rats

Abstract

Abstract FIP, is an abroad-spectrum phenylpyrazole insecticide, and/or its metabolites trigger the toxicity in liver via the mitochondrial respiratory chain inhibition. This work aimed to investigate the effect of vitamin D3 against FIP-induced liver toxicity in male rats. Vit. D3 attenuated liver markers, hepatic necrosis and inflammation, and dyslipidemia in FIP-intoxicated rats. Vit. D3 also reduced FIP-induced oxidative stress by increasing the activities of antioxidant enzymes, such as SOD, CAT, GPx, and GSH, and inhibiting lipid peroxidation products and nitric oxide levels in rat liver. Further investigations revealed that Vit. D3 counteracted FIP-induced increased levels of IL-6, TNF-α. Moreover, Vit. D3 up-regulated the AMPK-α, and PPAR-γ mRNA gene expression. In addition, Vit D3 improved the histopathological changes caused by FIP. In conclusion, Vit. D3 prevented liver damage in FIP-treated rats via augmentation of antioxidant defense mechanisms and inhibition of inflammatory cytokines/mediators and up-regulation of AMPK-α, and PPAR-γ.