Assessment of hepatoprotective and nephroprotective potential of withaferin A on bromobenzene-induced injury in Swiss albino mice: possible involvement of mitochondrial dysfunction and inflammation
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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.
KeywordsGlutathione Liver Mitochondria Anti-oxidant
The authors are thankful to the VIT University for the infrastructure and support provided for the research.
Compliance with ethical standards
Experimental procedure for the present study has been approved by the ethical committee (VIT/IAEC/VII th/17) of the VIT University, Vellore, India.
Conflict of interest
The authors declare that they have no conflict of interest.
- Bonting SL. Presence of enzyme system in mammalian tissues. In: Bilter EE, editor. Membrane and ion transport. London: Wiley Inter Science; 1970. p. 257–63.Google Scholar
- Dey D, Sunetra C, Nitin A, Deepa C. Acute and chronic toxicity, cytochrome P450 enzyme inhibition, and hERG channel blockade studies with a polyherbal, ayurvedic formulation for inflammation. Biomed Res Int. 2015; 1–9.Google Scholar
- Fiske CH, Subbarow Y. The colorimetric determination of phosphorus. J Biol Chem. 1925;66:375–400.Google Scholar
- Johnson D, Lardy H. Isolation of liver or kidney mitochondria. In: Methods in enzymology. London: Academic; 1981. p. 94–96.Google Scholar
- Reed LJ, Mukherjee RB. α-Ketoglutarate dehydrogenase complex from Escherichia coli. In: Colowick SP, Kaplon NO, editors. Methods in enzymology, vol. 13. New York: Academic; 1969. p. 53–61.Google Scholar
- Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1974;147:389–94.Google Scholar
- Szymanaska JA. Hepatotoxicity of brominated benzenes: relationship between chemical structure and hepatotoxic effects in acute intoxication of mice. Arch Toxicol. 1998;72:97–103.Google Scholar
- Yang J, Dongmei L, Weixin J, Hans-Uwe D, Lan WB. Effects of cadmium on lipid storage and metabolism in the freshwater crab Sinopotamon henanense. Plos One. 2013;8(10).Google Scholar