Abstract

ROLE OF AMINOPHYLLINE ON DOXORUBICIN-INDUCED CARDIOTOXICITY IN ANIMAL MODEL

Dr. Mrinal Pal*, Dr.Subinay Datta, Dr. Maloy Mandol , Dr. Ritabrata Mitra

ABSTRACT

Background: Doxorubicin is a potent chemotherapeutic drug The clinical usefulness of doxorubicin has been limited largely by the risk of cardiomyopathy and life-threatening heart failure. Cellular changes leading to this toxicity are suggested to be mediated through a druginduced increase oxidative stress. Aim: This study investigated the effects of aminophylline on doxorubicin-induced cardiotoxicity in rat due to its antioxidant property. Materials and methods: Thirty five healthy Wistar strain albino rats were used. They were divided randomly into 5 groups (7 animals in each group). All animals supplied with standard food during the experiment with an access of water. They were distributed as follow: first group (normal saline treated group, 1 ml/kg, i.p.) in six equal doses in alternative days over a period of 2 weeks and considered as control group. Second, doxorubicin treated group (2.5 mg/kg, i.p., in six equal doses in alternative days over a period of 2 weeks to make a total cumulative dose of 15 mg/kg, body weight). The third, fourth and fifth groups were treated with aminophylline in doses (10, 20 and 30 mg/kg, i.p.) respectively plus doxorubicin (one hour prior each administered dose of doxorubicin ). Blood samples were collected and used to determine the serum levels of cardiac biomarker cardiac specific troponin T in addition to oxidative stress parameters malondialdehyde (MDA) and superoxide dismutase (SOD). Results: In aminophylline plus doxorubicin treated groups serum levels of cardiac troponin T and MDA were significantly lower than those of doxorubicin-treated group, While plasma SOD was increase. These changes occurred in a dose-dependent manner. Conclusions: This suggests that aminophylline may have a role in the attenuation and prevention of the serious cardiac complications of doxorubicin.

Keywords: Aminophylline, Doxorubicin-induced cardiotoxicity, oxidative stress, antioxidant.