Cyclosporine A attenuates apoptosis and necrosis after ischemia-reperfusion-induced renal injury in transiently hyperglycemic rats

Abstract

Acute hyperglycemia is associated with increased morbidity and mortality in patients with trauma, cardiovascular collapse, and those subjected to heart surgery1 , due to increased oxidative stress in ischemic organs2-4. The choice of anesthetic techniques, with drugs that provide better protection against the effects of ischemia and reperfusion, has been studied particularly in renal transplantation using the general anesthesia technique with propofol or isoflurane5 . The mitochondrial permeability transition pore opening occurs within the initial minutes of reperfusion after ischemia and is associated with pathogenesis of necrosis and apoptosis and should be regarded as a determining step for reversible or irreversible cell death6. Inhibition of the mitochondrial permeability transition pore by cyclosporine A at the onset of reperfusion has been shown to protect the myocardium subjected to ischemia7,8. Krolikowski et al.9 demonstrated that keeping the mitochondrial permeability transition pore closed with cyclosporine A enhanced cardioprotection produced by isoflurane-induced postconditioning. Huhn et al.10 assessed the extent of myocardial infarct in rats after ischemia-reperfusion injury and demonstrated that hyperglycemia blocked sevoflurane-induced postconditioning, worsening the injury. They also showed that the inhibition of the mitochondrial permeability transition pore with cyclosporine A was able to reverse the loss of sevoflurane-induced postconditioning and cardioprotection10. Thus, we hypothesized that cyclosporine A could protect the ischemiareperfusion-induced renal injury during transiently hyperglycemia in a rat model under propofol or isoflurane anesthesia. In this study, we proposed to determine the effects of cyclosporine A in hyperglycemic rat kidneys subjected to ischemia-reperfusion injury under the exposition of either propofol or isoflurane.