Preventive effect of crocin of Crocus sativus on hemodynamic, biochemical, histopathological and ultrastuctural alterations in isoproterenol-induced cardiotoxicity in rats

We investigated the effects of crocin, a pharmacologically active constituent of Crocus sativus L., in isoproterenol (ISO)-induced cardiotoxicity with reference to hemodynamic, antioxidant, histopathological and ultrastructural parameters. Rats were administered crocin (5, 10 and 20 mg/kg/day) or vehicle orally for 21 days along with ISO (85 mg/kg, subcutaneously, at 24 h interval) on 20th and 21st day. On 22nd day ISO-control rats showed cardiac dysfunction as indicated by lowering of systolic, diastolic and mean arterial blood pressures. In addition, a significant decrease in maximum positive and negative rate of developed left ventricular pressure (±LVdp/dtmax) and an increase in left ventricular end-diastolic pressure (LVEDP) were observed. Furthermore, a marked reduction in the activities of myocardial creatine kinase-MB (CK-MB) isoenzyme, lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) levels along with an increase in content of malondialdehyde (MDA) were observed. Myocardial necrosis, edema and inflammation were evident from the light microscopic and ultrastructural changes. Crocin at the dose of 20 mg/kg/day significantly modulated hemodynamic and antioxidant derangements. The preventive role of crocin on ISO-induced MI was reconfirmed by histopathological and ultrastructural examinations. The effect at the dose of 20 mg/kg/day of crocin was more pronounced than that of other two doses (5 and 10 mg/kg/day). The results suggest that crocin may have cardioprotective effect in ISO-induced cardiac toxicity through modulation of oxidative stress in such a way that maintains the redox status of the cell.