The Protective Effects Of Carvedilol Against The Adriamycin-induced Cardiotoxicity

INTRODUCTION Anthracycline opens up a broad prospect for chemotherapy. Adriamycin was first introduced in the 1970s, and since that time has become one of the most commonly used anthracycline antibiotics for the treatment of both hematological and solid tumors. Although adriamycin is one of the most effective and useful antineoplastic agents for the treatment of a variety of malignancies, its repeated administration can induce irreversible myocardial damage. Its clinical usage is often limited by the undesirable acute and chronic side-effects. The acute side-effects such as myelosuppression, nausea, vomitting and arrhythmias are either reversible or clinically manageable. The chronic side-effects represented by the development of cardiomyopathy and ultimately congestive heart failure, which are irreversible and have bad prognosis. In a retrospective study of patient records, these cardiotoxic effects have been found to correlate with the total amount of the drug administered. Consequently, once the cumulative dose exee-ds 500mg/m~2, the cancer patients often were conflicted with adriamycin-induced cardiotoxicity, so, if we couldn' t protect the heart from adriamycin, it will be excluded from many chemotherapies. So, all kinds of ways were explored to relieve adriamycin cardiotoxicity while presserving antitumor activity of adriamycin. Oxidative stress and apoptosis are suggested to be involved in adriamycin cardiotoxicity curently. Carvedilol is a non-selective β-blocker with strong antiox-idant properties and with α-blocking properties, carvedilol has been shown to produce a reduction in mortality and approved for use incongestive heart failure. So, we examined the beneficial effects of carvediiol on adriamycin-induced cardiotoxicity. OBJECTIVE The study aims to explore the protective effects of carvediiol on the adriamycin-induced rat cardiotoxicity and to explore its possible mechanism.METHODS Wistar rats weighing 270+ lOg were randomly divided into three groups(n=12 in every group): adriamycin group, carvediiol group and control group. Adriamycin (2. 5 mg/kg) was administered to rats in eight equal intraperitoneal injections over a period of 2 weeks (cumulative dose of 20 mg/kg)in adriamycin group, normal saline (30 mg/kg daily) was administered orally in twe equal doses every days over a 8-week period. Carvediiol (30 mg/kg daily) was administered orally in two equal doses every day over a 8-week period with adriamycin treatment in carvediiol group. The equivalent volume of normal saline was used in control group. In 9 week, the changes of rat cardiac function, the activity of superoxide dismutase and the contents of malondialdehyde in serum as well as myocardial cell apoptosis were detected. RESULTS 1 Hemodynamic effects: Compared with control group, hemodyn-amic parameters in adriamycin group were deteriorated (P<0.05). Compared with adriamycin group, +dp/dtTOJ were increased (P<0. 05) and LVEDP was decreased (P<0. 05) in carvediiol group, but LVSP and MAP were not different from adriamycin group(P>0. 05). +dp / dtmM and LVEDP in carvediiol group and control group were not significant (P>0. 05) . 2 The activity of superoxide dismutase and the contents of malondialdehyde in serum: The activity of superoxide dismutase in carvediiol group were enhanced significantly compared with adriamycin group (P<0. 05), the contents of malondialdehyde in carvediiol group...