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Protective role of atorvastatin against doxorubicin-induced cardiotoxicity and testicular toxicity in mice
Authors:Ramanjaneyulu SVVS  P P Trivedi  S Kushwaha  A Vikram  G B Jena
Institution:2. Department of Toxicology, NCER&D, Piramal Healthcare Limited, Goregaon East, Mumbai, Maharashtra, 400 063, India
1. Facility for Risk Assessment & Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab, 160 062, India
3. Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, PA, 15213, USA
Abstract:Doxorubicin (DOX), a potent chemotherapeutic agent, is widely used for the treatment of various malignancies. However, its clinical uses are limited due to its dose-dependent adverse effects particularly cardiac and testicular toxicities. DOX-induced toxicity is mainly due to the induction of oxidative stress. Atorvastatin (ATV), a 3-hydroxy 3-methyl glutaryl coenzyme A reductase inhibitor, with lipid-lowering activity, acts as an antioxidant at lower doses. It possesses pleiotropic effects independent of cholesterol-lowering property usually shown at lower doses, which include antioxidant and anti-inflammatory activities. The present study was aimed to investigate the possible protection exerted by atorvastatin against oxidative stress and DNA damage induced by DOX in the heart and testes of mice. The protective role of ATV in the heart and testes of DOX-treated mice was evident from the amelioration of oxidative stress, DNA and cellular damage. The present study clearly indicates that ATV offers a significant protection against DOX-induced oxidative stress and DNA damage in the heart and testes of mice.
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