Protective Effect of Murraya koenigii Leaf Extract Against Doxorubicin Induced Cardiotoxicity

Abstract

Anthracyclines, including doxorubicin, are considered as the most effective anticancer treatment ever developed. The successful use of doxorubicin is hampered by toxicities such as hepatotoxicity and nephrotoxicity, yet the most feared side-effect is cardiotoxicity. Doxorubicin-induced cardiomyopathy is strongly linked to an increase in cardiac oxidative stress evidenced by reactive oxygen species-induced damage. It has been reported that Murraya koenigii (Karapincha) leaves have strong antioxidant potential. Objective of this study was to determine the protective effect of Murraya koenigii leaf extract against doxorubicin induced carditoxicity in Wistar rats at different dosages. Wistar albino rats were divided into seven groups of 10 animals in each. Group 1: normal control; Group 2: doxorubicin control (18 mg/kg, ip, after 16 hour fast on the 11th day); Groups 3-7: five doses of freeze dried aqueous leaf extracts (0.125, 0.25, 0.5, 1.0, 2.0g/kg, orally, daily for 14 days). Animals were sacrificed on the 15th day and blood was collected for estimation of serum concentrations of cardiac troponin I (cTnI), AST and LDH and myocardial tissues were collected for histopathological assessment. Mean cTnI concentrations of groups 1-7 were 0, 161.9, 88.51, 74.41, 34.54, 17.62 & 15.31pg/mL. In groups 1-7, mean AST activities were 26.82, 68.1, 42.52, 41.38, 28.69, 27.4 & 25.89U/L and LDH activities were 1166.13, 2428.84, 1285.31, 1204.09, 1195.66, 1177.45 & 1161.58U/L. A significant difference (P<0.05) between group 2 and groups 3-7 was evident in the mean concentration of all three cardiac biomarkers. A dose dependent reduction in the histopathological evidence of myocardial toxicity was observed with increasing dosage of plant extracts. According to the biochemical and histopathological assessment, Murraya koenigii leaf extract was protective against doxorubicin induced cardiotoxicity and administration of 2 g/kg dosage of the extract showed the highest effect.