Protective Effect of Ephedra nebrodensis on Doxorubicin-Induced Cardiotoxicity in Rats

Doxorubicin (DOX) is an anthracycline antibiotic with broad spectrum anti-tumour activity. Its effectiveness has been limited by the occurrence of dose-related myocardial and bone marrow toxicity. As oxidative stress is the main factor in DOX-induced cardiotoxicity, we presumed that agents which enhance endogenous antioxidants can prevent DOX induced cardiotoxicity. Animals received either DOX (3 mg/kg, i.p.) every other day or combination of Ephedra nebrodensis (100 mg/kg and 200 mg/kg, p.o.) and DOX or Ephedra nebrodensis (200 mg/kg, p.o.) extract alone for 2 weeks. Vitamin E (25 mg/kg, p.o.) was used as a positive standard. Cardiotoxicity was assessed by recording changes in ECG (increased QT interval), measuring the levels of cardiac marker enzymes such as lactic acid dehydrogenase (LDH), creatine phosphokinase (CPK), glutamic oxaloacetic transaminase (GOT), and the antioxidant defence enzyme such as reduced glutathione (GSH), superoxide dismutase (SOD), and lipid peroxidative value (LPO) at the end of treatment schedule. Changes in heart rate were also measured in all groups. Treatment with Ephedra nebrodensis (100 mg/kg and 200 mg/kg) significantly ( p <0.05) decreased the levels of LPO and cardiac marker enzymes, increased the levels of other antioxidant defence enzymes, GSH and SOD, reversed the changes in ECG and prevented the decrease in heart weight in DOX-treated group. The results suggest that Ephedra nebrodensis has the potential in preventing the cardiotoxic effects induced by Doxorubicin.