Diosgenin-induced protection against myocardial ischaemia-reperfusion injury is mediated by mitochondrial KATP channels in a rat model.

Abstract

This study was aimed to evaluate the effects of diosgenin on myocardial ischaemia-reperfusion injury and the potential involvement of mitochondrial KATP (mitoKATP) channel and nitric oxide (NO) system blockades in this field. After isolation of hearts of male Wister rats, the study was conducted on control and diosgenin- receiving hearts in the presence or absence of 5-HD and L-NAME (as antagonists of mitoKATP channel and NO system, respectively) in an isolated buffer-perfused heart model. Global ischaemia was induced by 30-min occlusion of aortic flow followed by 90-min reperfusion. Cardiac haemodynamics were recorded throughout the experiment using a PowerLab data acquisition system. The levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) in the coronary effluents were estimated colourimetrically. Diosgenin pre-administration significantly decreased the release of LDH and CK-MD into the coronary effluent as compared the with the control group (P < 0.05). The left ventricular developed pressure (LVDP) and contractility (± dP/dt) were significantly improved and restored to pre-ischaemic values in the diosgenin-receiving group (P < 0.05). There were no significant differences in left ventricular end-diastolic pressure, coronary flow and heart rate between the control and diosgenin-treated groups during the pre-ischaemic and reperfusion periods. Blocking the mitoKATP channels by 5-HD completely eliminated the positive effect of the diosgenin on the LVDP and ± dP/dt (P < 0.05). However, blocking the NO system by L-NAME slightly reduced the diosgenin effects and the inhibitory effect of L-NAME was less than 5-HD. The results showed that diosgenin may have cardioprotective effects against myocardial reperfusion injury through activating the mitoKATP channels.