Effect of Ethanolic Extract Fractions of Boerhaavia diffusa in Doxorubicin-induced Myocardial Toxicity in Albino Rats

Abstract

: Background: Doxorubicin is a Anthracycline derivative and has proven efficacy in various malignancies. It is the most effective cytotoxic agent in current use. The clinical usefulness is limited due to its cardiac toxicity. Objectives: To study the preventive role of ethanolic extract fractions of Boerhaavia diffusa (BD) against doxorubicin (Dox) induced myocardial toxicity in albino rats. Methods: The ethanolic extract of whole plant of Boerhaavia diffusa was prepared by hot extraction method and further fractionated into Petroleum ether (PEBD), Chloroform (CLBD), Ethyl acetate (EABD) and Aqueous (AQBD) fractions by increasing in order of polarity. Cardiotoxicity was produced by cumulative administration of Dox (2.5 mg/kg, i.p. alternative day for two weeks). All four fractions (PEBD-20 mg/kg, CLBD-25 mg/kg, EABD-30 mg/kg and AQBD-25 mg/kg) and vitamin E as standard (100 mg/kg) were administered orally as pretreatment for two weeks followed by Dox on alternative days for two weeks. The general observations, biomarker enzymes like lactate dehydrogenase (LDH), Creatine kinase (CK-MB) and Troponin-I (cTnI), biochemical parameters such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were monitored after three weeks of last dose. Myocardial toxicity was also evaluated by histopathologic studies. Results: Repeated administration of Dox-induced cardiomyopathy characterized with an increased level of biomarkers and antioxidant deficit. Pretreatment with the EABD and Vit-E significantly protected myocardium from the toxic effects of Dox by reducing the elevated level of biomarker enzymes like LDH, CK-MB, biochemical parameters such as AST and ALT, absence of cTnI and restoring of disorganized myocardial tissue to normal. Conclusion: The biomarker, biochemical and histopathological data evidently substantiate the cardioprotective effect of EABD, which could be attributed to flavanoids present in the ethyl acetate fraction.Key words: Boerhaavia Diffusa, Cardiotoxicity, Doxorubicin, Troponin-I, CKMB.