Abstract

Abstract Doxorubicin is a very potent drug with broad spectrum of biological activity, used to treat a wide variety of human malignancies and many solid tumors. The clinical efficacy of drug in a wide range of malignant disorders is hampered by its dose limiting side effects such as nephrotoxicity and cardiotoxicity. The effect of intraperitoneal injection of doxorubicin at dose level of 2 mg/kg body weight 2 days/week without or with oral administration of navel orange peel ethanolic extract or naringin at dose level of 50 mg/kg body weight dissolved in 1% carboxy methyl cellulose every other day for six weeks was evaluated in adult male rats. Serum levels of urea, uric acid, and creatinine as well as activities of creatine kinase-MB, lactate dehydrogenase and aspartate aminotransferase were determined. Lipid peroxidation (indexed by MDA), glutathione content and glutathione peroxidase activity in kidney and heart were also detected. The treatment of doxorubicin-administered rats with navel orange peel ethanolic extract or naringin significantly ameliorated the elevated serum creatinine, urea and uric acid concentration reflecting improvement of kidney function. Similarly, the heart function in doxorubicin-administered rats was alleviated as a result of treatments as manifested by decrease of the elevated creatine kinase-MB, lactate dehydrogenase and aspartate aminotransferase activities. The perturbed histological changes in kidney and heart were markedly amended due to the treatments of doxorubicin-administered rats. Moreover, the treatment with navel orange peel ethanolic extract or naringin reduced doxorubicin-induced elevation in lipid peroxidation and suppression of glutathione content and glutathione peroxidase activity. In conclusion, it can be supposed that navel orange peel ethanolic extract and naringin may provide a cushion for a prolonged therapeutic option against doxorubicin toxicity without harmful side effects. However, further clinical studies are required to assess the safety and efficacy of these extract in human beings.

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