Amelioration of bromobenzene hepatotoxicity by Withania somnifera pretreatment: Role of mitochondrial oxidative stress

•Administration of bromobenzene to rats caused increased levels of liver marker enzymes, lipid peroxidation, TNF-α, IL-1β, VEGF, depletion in levels of mitochondrial enzymes and antioxidants.•Pre-treatment with Withania somnifera normalized the levels of liver marker enzymes, TNF-α, IL-1β, VEGF, mitochondrial enzymes, antioxidants and ameliorated histopathological manifestations in bromobenzene-treated rats.•Molecular dockings studies showed strong interactions between pro-inflammatory mediator NF-ƙB and various active components of W. somnifera (Withaferin A, Withanolide D and Withanolide E), thus blocking it from causing progressive tissue damage.

The present study investigated the possible protective role of Withania somnifera (Linn.) Dunal (Solanaceae) root powder against bromobenzene-induced oxidative damage in rat liver mitochondria. Administration of bromobenzene (10 mmol/kg body weight) to rats resulted in increased levels of liver marker enzymes, lipid peroxidation, TNF-α, IL-1β and VEGF. There was also marked depletion in the levels of mitochondrial enzymes and antioxidant activity. Pre-treatment with W. somnifera significantly decreased the levels of liver marker enzymes, TNF-α, IL-1β, VEGF and ameliorated histopathological manifestations in bromobenzene-treated rats. The molecular docking analysis predicted that the pro-inflammatory mediator NF-κB showed significant interaction with selected various active components of W. somnifera (withaferin A, withanolide D and withanolide E). This study demonstrates a good protective effect of W. somnifera against bromobenzene-induced oxidative stress.

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