Effect of probucol and desferroxamine against adriamycin toxicity in cardiac and renal tissues of rats

Abstract

Adriamycin (ADR) is an anthracycline glycoside with a broad spectrum of therapeutic activity against various tumors; however, its clinical use has been limited due to its cardiac and renal toxicity. Production of free radicals is involved in the development of ADR-induced toxicity. This study investigated the effect of pre-treatment with probucol (PROB, a hypolipidemic drug with a powerful antioxidant property) and desferroxamine (DFO, an iron chelator) against ADR-induced oxidative stress in the cardiac and renal tissues. Forty male Wistar rats were divided into four groups: Group I rats received ADR (3 mg/kg, b.w i.p.) over a period of 2 weeks for a cumulative dose of 18 mg/kg, b.w; Group II or ADR + PROB group rats were given PROB i.p. in a cumulative dose of 120 mg/kg, b.w. divided into twelve equal injections over a period of 4 weeks starting 2 weeks before ADR administration; Group III or ADR + DFO group rats were given DFO i.p. in six equal doses each 50 mg/kg, b.w.over a period of 2 weeks given 30 min before ADR injection; and Group IV rats were kept without treatment and served as a control. Results showed that ADR administration caused a significant increase in malondialdehyde (MDA) level in serum, heart and kidney tissues along with lowered activities of cardiac and renal glutathione peroxidase (GPx) and glutathione-S-transferase (GST). A significant decrease in cardiac glutathione (GSH) level and xanthine dehydrogenase (XD)/xanthine oxidase (XO) ratio, serum creatine kinase (CK) and renal glutathione reductase (GR) activities was also observed. Cytotoxic damage was evident from the histopathological examination in heart and kidney specimens. Pre-treatment with either PROB or DFO restored the cardiac, renal and serum MDA levels and renal GR and cardiac GST activities. They also caused significant elevation in serum CK activity and renal XD/XO ratio. PROB normalized the activity of cardiac GPx, whereas DFO restored activity of GPx in both cardiac and renal tissues. It can be concluded that pre-treatment with either PROB or DFO counteracts the state of oxidative stress associated with ADR treatment by modulating the antioxidant status of the animals.