Protective effect of aminophylline on doxorubicin-induced cardiotoxicity in rats

Abstract EN

Background : doxorubicin is a highly effective antitumor drug, however its usefulness is limited due to its ability to induce cardio toxicity.

Cellular changes leading to this toxicity are suggested to be mediated through a drug-induced increase in free radicals and lipid peroxidation.

Aim of study : to evaluate the protective properties of aminophylline on doxorubicin-induced cardiotoxicity in rats using biochemical approaches.

Materials and methods : Thirty five healthy male Swiss 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 {Lactate Dehydrogenase (LDH), Creatine Kinase (CK-MB) and troponin I} in addition to oxidative stress parameters {malondialdehyde (MDA) and glutathione (GSH)}.

Results : in aminophylline plus doxorubicin treated groups serum levels of LDH, CK-MB, troponin I and MDA were significantly lower than those of doxorubicin-treated group, While serum GSH was increase.

These changes occurred in a dose-dependent manner.

Conclusions : these data show that aminophylline can provide a protective effect against doxorubicin cardiomyopathy.

This protective effect of aminophylline may be attributed to its enhancing effect on cellular cyclic nucleotides antioxidant defense on the heart.