Diosgenin-induced protection against myocardial ischaemia-reperfusion injury is mediated by mitochondrial KATP channels in a rat model.
Perfusion. 2015 Oct ;30(7):565-71. Epub 2014 Dec 31. PMID: 25552273
OBJECTIVE: 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.
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 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.
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 (± 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.
CONCLUSION: The results showed that diosgenin may have cardioprotective effects against myocardial reperfusion injury through activating the mitoKATP channels.