The grape fruit flavonone naringin protects mice against doxorubicin-induced cardiotoxicity

Ganesh Chandra Jagetia, Tiyagura Koti Reddy


Doxorubicin (DOX), an anthracycline drug widely used for the treatment of various cancers, causes a cumulative dose-dependent cardiac toxicity that is characterized by an irreversible cardiomyopathy and congestive heart failure. The cardioprotective effect of 2.5, 5, 7.5 and 10 mg/kg naringin (NIN) was studied in mice treated with 15 mg/kg DOX. The animals were killed 30 h after DOX treatment. The latter induced acute cardiotoxicity indicated by a significant elevation in glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase (CK-MB) and lactate dehydrogenase (LDH) in mice serum. Treatment of mice with NIN before DOX administration significantly reduced serum levels of GPT, GOT, CK-MB and LDH indicating that NIN protected against the DOX-induced cardiotoxicity. DOX induced a significant increase in the 8-OHdG DNA adducts and the PARP activity in the heart and liver of mice, whereas NIN treatment of mice before DOX administration significantly reduced 8-OHdG DNA adducts and PARP activity in the heart and liver. Similarly, NIN inhibited the DOX-induced decline in the glutathione concentration, catalase and superoxide dismutase activities and abated DOX-induced lipid peroxidation in the heart and liver of mice. Intraperitoneal administration of 1.25 mg/kg DOX significantly elevated survival of Ehrlich ascites carcinoma (EAC) bearing mice, whereas the combination of 10 mg/kg NIN with DOX did not alter the tumor cell growth, median survival time or average survival time of tumor bearing mice when compared to DOX treatment alone, indicating that NIN does not interfere with the antineoplastic activity of DOX. Our study demonstrates that naringin reduced the doxorubicin-induced cardiotoxicity, without affecting its antineoplastic activity, which may be due to reduction in the DOX-induced 8-OHdG DNA adducts and PARP activity, increase in the antioxidant enzymes and alleviation of lipid peroxidation by naringin.


Doxorubicin; mice; cardiotoxicity; glutathione; PARP; DNA adducts


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