Bioactive Extract of Morel Mushroom, Morchella esculenta (Ascomycota) Attenuates Doxorubicin-Induced Oxidative Stress Leading to Myocardial Injury.

Abstract

Doxorubicin (DOX) is an extensively used anticancer drug for chemotherapy. Cardiotoxicity induced by DOX is an impediment in its clinical use. The aim of the current study is to evaluate the effect of a bioactive extract of an excellently edible morel mushroom, Morchella esculenta (ME) to attenuate DOX - induced cardiotoxicity. Protective effect of ME against DOX-induced cytotoxicity was evaluated in vitro by MTT assay using H9C2 cardiomyoblast cells. Intracellular free radical generation and mitochondrial membrane damage caused by DOX were detected by DCF-DA and rhodamine-123 dyes. Elevation of activities of creatine kinase-MB, lactate dehydrogenase and troponin I level consequent to the administration of DOX were determined using diagnostic kits. Depletion of endogenous antioxidant levels in myocardium was determined by spectrophotometric assays. Cardiac tissue damage caused by DOX was assessed by histopathological examination. ME reduced cytotoxicity caused by DOX at concentrations of 150 and 200 μg (p < 0.05 and p < 0.01, respectively). Cardiac injury marker levels elevated by DOX were significantly down regulated by ME (p < 0.01). Endogenous antioxidants such as SOD, GPx, and GSH depleted by DOX administration were restored to almost normal level by ME. This indicated the effect of ME to ameliorate oxidative stress caused by DOX administration leading to myocardial injury. Histopathological observation supported the finding. Being an excellently edible mushroom, current study indicates the potential therapeutic use of M. esculenta to prevent DOX-induced cardiotoxicity. The findings also suggest the clinical use of this medicinal mushroom to prevent chemo drug-induced cardiotoxicity.