Diosgenin-induced protection against myocardial ischaemia-reperfusion injury is mediated by mitochondrial K<inf>ATP</inf> channels in a rat model

Abstract

Objective: This study was aimed to evaluate the effects of diosgenin on myocardial ischaemia-reperfusion injury and the potential involvement of mitochondrial K<inf>ATP</inf> (mitoK<inf>ATP</inf>) channel and nitric oxide (NO) system blockades in this field. Materials and methods: 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 mitoK<inf>ATP</inf> 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. Results: 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 (آ±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 mitoK<inf>ATP</inf> channels by 5-HD completely eliminated the positive effect of the diosgenin on the LVDP and آ±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. Conclusion: The results showed that diosgenin may have cardioprotective effects against myocardial reperfusion injury through activating the mitoK<inf>ATP</inf> channels. é The Author(s) 2015.