title: Assessment of hepatoprotective and nephroprotective potential of withaferin A on bromobenzene-induced injury in Swiss albino mice: possible involvement of mitochondrial dysfunction and inflammation.
abstract: Bromobenzene is a well-known environmental toxin which causes liver and kidney damage through CYP450-mediated bio-activation to generate reactive metabolites and, consequently, oxidative stress. The present study aimed to evaluate the possible protective role of withaferin A against bromobenzene-induced liver and kidney damage in mice. Withaferin A (10 mg/kg) was administered orally to the mice for 8 days before intragastric intubation of bromobenzene (10 mmol/kg). As results of this experiment, the levels of liver and kidney functional markers, lipid peroxidation, and cytokines (TNF-α and IL-1β) presented an increase and there was a decrease in anti-oxidant activity in the bromobenzene-treated group of mice. Pre-treatment with withaferin A not only significantly decreased the levels of liver and kidney functional markers and cytokines but also reduced oxidative stress, as evidenced by improved anti-oxidant status. In addition, the mitochondrial dysfunction shown through the decrease in the activities of mitochondrial enzymes and imbalance in the Bax/Bcl-2 expression in the livers and kidneys of bromobenzene-treated mice was effectively prevented by pre-administration of withaferin A. These results validated our conviction that bromobenzene caused liver and kidney damage via mitochondrial pathway and withaferin A provided significant protection against it. Thus, withaferin A may have possible usage in clinical liver and kidney diseases in which oxidative stress and mitochondrial dysfunction may be existent.
authors.affiliation: SBST, VIT University, Vellore, Tamil Nadu, 632014, India.
authors.forename: Mahima
authors.initials: M
authors.lastname: Vedi
authors.affiliation: SBST, VIT University, Vellore, Tamil Nadu, 632014, India. eps674@gmail.com.
authors.forename: Evan Prince
authors.initials: EP
authors.lastname: Sabina
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001969:Bromobenzenes / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D054358:Withanolides / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D001969:Bromobenzenes; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D054358:Withanolides; C032036:bromobenzene; C009684:withaferin A
keywords: Anti-oxidant; Glutathione; Liver; Mitochondria