Evaluation of Fractions of Artocarpus lakoocha R. on Doxorubicin Induced Myocardial Toxicity in Wistar Rats

ABSTRACT

Background: Doxorubicin, an anthracycline derivative, is a cytotoxic drug that has been shown to be effective against a variety of cancers. Its clinical utility has been limited due to dose-dependent cardiac toxicity. Objectives:To fractionate the ethanolic extract of bioactive Artocarpus lakoocha Roxb. bark and to Phytochemical investigation of fractions and pharmacological evaluation on doxorubicin induced cardiotoxicity in rats. Materials and Methods: In vitro studies conducted to determine Cardioprotective activity of the fractions of ethanolic plant extract. Cardiotoxicity induced with DOX (2.5 mg/kg body weight i.p) in 6 equal injections given alternatively for 2 weeks to make a total cumulative dose of 15 mg/kg body weight. Comparative studies were done between Treatment group, Dox 2.5 mg/kg on alternative day for 2 weeks followed by fractionation method-Petroleum ether fraction (11.2 mg/kg), Chloroform fraction (66 mg/kg), Ethyl acetate fraction (34 mg/kg) and aqueous fraction (44.4 mg/kg) of Artocarpus lakoocha R. for 2 weeks. Animals were observed for change in body weight, food and water intake ECG changes, hematology analysis such as RCB, WBC, Platelet, hematocrite level, Cardiac markers such as CK-MB, LDH and cTn I, Antioxidant enzymes such as GSH, Catalases, SOD and MDA were monitored. Heart histopathological studies carried out to evaluate cardiotoxicity. Results: As a result of Dox treatment, cardiomyopathy develops, which is characterized by an increase in cardiac biomarkers, changes in ECG, hematology analysis and a deficiency in antioxidant enzymes. By lowering the elevated levels of biomarker enzymes like LDH and CK-MB and the absence of CTnl, Fractions of EAAL significantly protected the myocardium from the toxic effects of Dox. Conclusion: Based on results of general appearance, hematology analysis, ECG studies, specific cardiac markers and antioxidant activity, it is concluded that the ethyl acetate fraction of Artocarpus lakoocha R. exhibited cardioprotective activity. Based on data obtained, treatment studies were found more effective when compared with preventive studies. Phytocompounds present in the plant is responsible for the cardioprotective activity.

KEYWORDS

• Artocarpus lakoocha R
• cardiotoxicity
• Doxorubicin
• Oxidative stress
• Rats

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• DOI10.5530/pres.16.4.102Copy

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