title: Preconditioning with sodium arsenite inhibits apoptotic cell death in rat kidney with ischemia/reperfusion or cyclosporine-induced Injuries. The possible role of heat-shock protein 70 as a mediator of ischemic tolerance.
abstract: This study was performed to evaluate the effect of heat-shock protein (HSP)70 induction with sodium arsenite (SA) on ischemia/reperfusion (I/R) or cyclosporin A (CsA)-induced injuries in rat kidney. Rats were classified into five groups (sham, I/R, SA+I/R, I/R+CsA and SA+I/R+CsA groups) according to both the status of SA pretreatment and treatment with CsA. SA (6 mg/kg, i.v.) pretreatment was accomplished 12 h before I/R injury, and CsA (20 mg/kg, s.c.) was given subsequent to I/R injury. The effect of SA pretreatment on I/R injury was evaluated using measurements of renal function, the histopathology score, and assays for apoptosis (DNA fragmentation analysis, TUNEL staining, mRNA expressions of the pro-apoptotic genes and caspase activities). In addition, mitochondrial morphology was examined by electron microscopy. Induction of HSP70 with SA improved both renal function and the histopathology score as compared to the group without HSP70 induction. The assays for apoptosis revealed that SA pretreatment decreased the DNA laddering pattern, TUNEL-positive cells, mRNAs expression of pro-apoptotic genes and caspase activities as compared with the group without SA pretreatment. In addition, the mitochondrial morphology was well preserved in the groups with SA pretreatment. In conclusion, SA pretreatment prevents subsequent I/R or CsA-induced injuries in the rat kidney, and this renoprotective effect appears to be mediated by induction of HSP70.
authors: Department of Internal Medicine, The College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors: C W
authors: CW
authors: Yang
authors: B S
authors: BS
authors: Kim
authors: J
authors: J
authors: Kim
authors: H J
authors: HJ
authors: Ahn
authors: J H
authors: JH
authors: Park
authors: D C
authors: DC
authors: Jin
authors: Y S
authors: YS
authors: Kim
authors: B K
authors: BK
authors: Bang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D018053:Arsenites / Q000627:therapeutic use*; D020169:Caspases / Q000378:metabolism; D016572:Cyclosporine; D053938:DNA Fragmentation; D015870:Gene Expression / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D019194:Ischemic Preconditioning; D007668:Kidney / Q000098:blood supply* / Q000737:chemistry / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D007683:Kidney Tubular Necrosis, Acute / Q000517:prevention & control; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control; D017670:Sodium Compounds / Q000627:therapeutic use*
chemical_list: D018053:Arsenites; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D017670:Sodium Compounds; C017947:sodium arsenite; D016572:Cyclosporine; D020169:Caspases