Protective Efficacy of Nardostachys jatamansi (Rhizomes) on Mitochondrial Respiration and Lysosomal Hydrolases during Doxorubicin Induced Myocardial Injury in Rats

摘要

Doxombicin is highly effective in treatment for several forms of cancer. However, doxorubicin induces a cumulative and dose dependent cardiomyopathy that has been ascribed to redox-cycling of the molecule on the mitochondrial complex 1 generating in the process of increased oxidative stress. In the search of new potential cardioprotective agents, the present study is directed to explore the effect of ethanolic extract of Nardostachys jatamansi on the mitochondrial and lysosomal damage induced by doxorubicin in rats. Heart mitochondria were isolated from rats treated with doxorubicin (15 mg/kg, ip) a single dose, exhibited depressed rates of state 3 respiration, low respiratory control ratio (RCR), decreased Oxidative Phosphorylation ratio, Adenosine Triphosphate content and cytochromes (c, c_1, b, aa_3). In addition the doxorubicin given rats showed significant changes in the lysosomal enzymes (Cathepsin-D, Acid phosphatase, beta-D-glucoronidase, beta-D-galactosidase and beta-N-acetyl glucosaminidase) and membrane bound phosphatases. Also myocardial damage, as assessed by ultrastructural changes showed loss of myofibrils, mitochondrial swelling, and cytoplasmic vacuolization. Pretreatment with Nardostachys jatamansi (500 mg/kg body weight orally) for seven days ameliorated the observed abnormalities and significantly prevented the mitochondrial respiration, lysosomal integrity, membrane bound phosphatases and ultrastructural studies in doxorubicin induced rats. These findings suggest that the cardioprotective efficacy of Nardostachys jatamansi could be mediated possibly through its antioxidant effect as well as by the attenuation of the oxidative stress.