Preconditioning with Sodium Arsenite Inhibits Apoptotic Cell Death in Rat Kidney with Ischemia/Reperfusion or Cyclosporine-Induced Injuries

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.