Cardioprotective Effect of Naringin in Mice Treated with Doxorubicin

The cardioprotective activity of Naringin (NIN), a grapefruit flavanone was evaluated against the doxorubicin-induced cardiotoxicity in mice. Increasing concentrations of NIN was given to mice (oral) for 5 days before intraperitoneal injection of 15 mg/kg doxorubicin (DOX). The animals were sacrificed 30 hours after DOX treatment. Serum lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) were estimated. The livers and hearts were excised and used for the estimation of 8-hydroxy-2ʹ-deoxyguanosine (8-OHdG), Poly (ADP-ribose) polymerase (PARP), antioxidant and histopathology analysis. DOX-treatment-induced a significant elevation in the serum levels of GPT, GOT, CK-MB and LDH, in mice indicating acute cardiotoxicity. Prior exposure of mice to NIN before DOX administration significantly reduced serum levels of GPT, GOT, CK-MB and LDH indicating that NIN protected against the DOX-induced cardiotoxicity. Oral administration of NIN to mice before DOX administration significantly reduced the levels of 8-OHdG and the activity of PARP in the heart and liver. Pretreatment of mice with various doses of NIN inhibited the DOX-induced decline in the antioxidant status of heart and liver. In a separate experiment the effect of NIN in altering the anticancer activity of doxorubicin was determined in the Ehrlich ascites carcinoma (EAC) mouse model. Intraperitoneal injection of 1.25 mg/kg DOX once daily for 9 days, significantly improved the survival of mice bearing Ehrlich ascites carcinoma (EAC). NIN alone did not exert any antitumor effect as the survival of tumor bearing mice was unaffected. Similarly, treatment of tumor bearing mice with 10 mg/kg body weight before DOX treatment did not alter the tumor cell growth, median survival time or average survival time of tumor bearing mice indicating that NIN does not interfere with the antineoplastic activity of DOX. The present study demonstrates that NIN protects mice against the DOX-induced cardiotoxicity, without altering the antineoplastic activity of DOX.