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Chronic unpredictable stress exacerbates 7,12-dimethylbenz (a) anthracene induced hepatotoxicity and nephrotoxicity in Swiss albino mice

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Abstract

Oxidative stress, a pervasive condition induced by stress has been implicated and recognized to be a prominent feature of various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) on hepatic and renal toxicity in terms of alterations of various in vivo biochemical parameters, oxidative stress markers and the extent of DNA damage in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12-dimethylbenz (a) anthracene (DMBA) alone (topical), DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical), and exposure to CUS prior to DMBA or DMBA-TPA treatment, and sacrificed after 16 weeks of treatment. Prior exposure to CUS increased the pro-oxidant effect of carcinogen as depicted by significantly compromised levels of antioxidants; superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, reduced glutathione in hepatic and renal tissues accompanied by a significant elevation of thiobarbituric acid reactive species (TBARS) as compared to DMBA alone or DMBA-TPA treatments. Loss of structural integrity at the cellular level due to stress-induced oxidative damage was demonstrated by significant increases in the hepatic levels of intracellular marker enzymes such as glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase, and significantly reduced levels of uric acid in kidney tissues. The results of DNA damage studies further positively correlated with all the above biochemical measurements. Thus, exposure to physical or psychological stress may significantly enhance the hepatotoxic and nephrotoxic potential of carcinogens through enhanced oxidative stress even if the treatment is topical.

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Acknowledgments

Thanks are due to University Grants Commission (UGC), New Delhi for financial support to the authors (Nida Suhail, Nayeem Bilal, and Shirin Hasan) in the form of a scholarship. The authors are grateful to UGC-SAP, DST-FIST, and Aligarh Muslim University for the facilities.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University (AMU), Aligarh, Uttar Pradesh, India

    Nida Suhail, Nayeem Bilal, Shirin Hasan & Naheed Banu

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  1. Nida Suhail
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  2. Nayeem Bilal
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  3. Shirin Hasan
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  4. Naheed Banu
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Correspondence to Naheed Banu.

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Suhail, N., Bilal, N., Hasan, S. et al. Chronic unpredictable stress exacerbates 7,12-dimethylbenz (a) anthracene induced hepatotoxicity and nephrotoxicity in Swiss albino mice. Mol Cell Biochem 355, 117–126 (2011). https://doi.org/10.1007/s11010-011-0845-y

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  • DOI: https://doi.org/10.1007/s11010-011-0845-y

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