title: Blocking of the ATP sensitive potassium channel ameliorates the ischaemia-reperfusion injury in the rat testis.
abstract: There is increasing evidence that the effects of administered ATP sensitive potassium (KATP ) channel openers or blockers during ischaemia are still controversial in many organs/tissues. Testicular torsion detorsion which causes ischaemia-reperfusion (IR) injury, cannot be predicted, thus an effective drug should be administered during or after the ischaemia. The aim of this study was to examine whether the administration of KATP channel openers or blockers during ischaemia ameliorates IR injury in the testis. Eight-week-old male Sprague-Dawley rats were subjected to 2 h right testicular ischaemia followed by 24 h reperfusion. The selective mitochondrial (mito) KATP channel blocker, 5-hydroxydecanoate (5-HD) (40 mg/kg), the non-selective KATP channel blocker glibenclamide (5 mg/kg), the selective mito KATP channel opener diazoxide (10 mg/kg) and the non-selective KATP channel opener cromakalim (300 μg/kg) were administered intraperitoneally 15 min prior to the ischaemia or 75 min after the induction of ischaemia. Tissue damage was evaluated by malondialdehyde concentration, myeloperoxidase activity, histological evaluation and TdT-mediated dUTP nick end labelling assay in the testis. There was a significant increase in oxidative stress, neutrophil infiltration, histological damage and apoptosis in the testicular IR model. A significant reduction in the testicular IR injury was observed with the administration of glibenclamide, but not 5-HD, diazoxide or cromakalim during ischaemia. The administration of non-selective KATP channel blocker glibenclamide ameliorated the testicular IR injury. On the other hand, the selective mito KATP channel blocker, 5-HD and KATP channel openers did not reduce the testicular IR injury. These data suggest that blocking of the membrane KATP channel may have a protective effect during the testicular ischaemia. Glibenclamide could be an effective drug to manage the post-ischaemic injury caused by the testicular torsion-detorsion.
authors.affiliation: Division of Molecular Pharmacology, Tottori University School of Medicine, Yonago, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shimizu
authors.forename: R
authors.initials: R
authors.lastname: Oikawa
authors.forename: P
authors.initials: P
authors.lastname: Tsounapi
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: D T
authors.initials: DT
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: T
authors.initials: T
authors.lastname: Sejima
authors.forename: S
authors.initials: S
authors.lastname: Tomita
authors.forename: M
authors.initials: M
authors.lastname: Saito
mesh_terms: D000818:Animals; D017209:Apoptosis; D019806:Cromakalim / Q000627:therapeutic use; D003652:Decanoic Acids / Q000627:therapeutic use; D003981:Diazoxide / Q000627:therapeutic use; D005905:Glyburide / Q000627:therapeutic use; D006880:Hydroxy Acids / Q000627:therapeutic use; D054086:KATP Channels / Q000819:agonists* / Q000037:antagonists & inhibitors*; D008297:Male; D008315:Malondialdehyde / Q000037:antagonists & inhibitors; D020556:Neutrophil Infiltration; D018384:Oxidative Stress; D009195:Peroxidase / Q000032:analysis; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013086:Spermatic Cord Torsion / Q000473:pathology*; D013737:Testis / Q000473:pathology*
chemical_list: D003652:Decanoic Acids; D006880:Hydroxy Acids; D054086:KATP Channels; D026902:Potassium Channel Blockers; D019806:Cromakalim; D008315:Malondialdehyde; C052853:5-hydroxydecanoic acid; D009195:Peroxidase; D003981:Diazoxide; D005905:Glyburide
keywords: adenosine triphosphate sensitive potassium channel; ischaemia-reperfusion; ischaemic postconditioning; rat; testicular torsion