title: Diosgenin-induced protection against myocardial ischaemia-reperfusion injury is mediated by mitochondrial KATP 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 KATP (mitoKATP) channel and nitric oxide (NO) system blockades in this field.
  
  
  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.
  
  
  CONCLUSIONS
  The results showed that diosgenin may have cardioprotective effects against myocardial reperfusion injury through activating the mitoKATP channels.
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: R
authors.initials: R
authors.lastname: Badalzadeh
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran yousefib@tbzmed.ac.ir.
authors.forename: B
authors.initials: B
authors.lastname: Yousefi
authors.affiliation: Student Research Committee, Tabriz University of Medical Sciences,Tabriz, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Tajaddini
authors.affiliation: School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: N
authors.initials: N
authors.lastname: Ahmadian
mesh_terms: D000818:Animals; D004144:Diosgenin / Q000494:pharmacology*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D004144:Diosgenin
keywords: cardiovascular; diosgenin; ischaemia-reperfusion injury; mitochondrial KATP channels; nitric oxide