Treatment with Risperidone Attenuates Oxidative Stress in the Kidney after Whole-Body Ischemia and Reperfusion Injury Induced by Cardiac Arrest in Rats

Abstract

Background: Whole-body ischemia and reperfusion (IR) injury following the return of spontaneous circulation (ROSC) after cardiac arrest (CA) can cause multiple organ dysfunction syndrome accompanied by adverse outcomes, including serious mortality. Renal IR injury following ROSC after CA is associated with complicated pathological processes. Renal IR injury is commonly observed in inpatients with heart failure and is associated with high mortality. Risperidone (Risp), an atypical antipsychotic drug, has been reported to exert beneficial effects against IR. This study investigated whether treatment with risperidone enhanced survival rates and reduced kidney failure following CA-induced whole-body IR injury. Methods: Rats were subjected to asphyxial CA for five minutes followed by ROSC induction, and risperidone (10 mg/kg) or saline was intravenously injected. Survival rate was evaluated using Kaplan-Meier survival analysis was used to evaluate the survival rate. Changes in serum levels of creatinine, lactate dehydrogenase (LDH), and blood urea nitrogen (BUN) were assessed. We carried out hematoxylin and eosin staining and immunohistochemistry for 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2′-deoxyguanosine (8-OHdG), superoxide dismutase 1 (SOD-1), and superoxide dismutase 2 (SOD-2). Results: Treatment with risperidone significantly improved the survival rate after CA and attenuated LDH, creatinine, and BUN levels. Histopathological injury was remarkably improved in the renal cortex following risperidone treatment including a significant attenuation of the immunoreactivities of 4-HNE and 8-OHdG. Conversely, immunoreactivities of SODs were significantly improved by risperidone treatment. Conclusions: The current results demonstrated that treatment with risperidone reduced the CA-induced renal injury by reducing oxidative stress and retaining antioxidant enzymes, which significantly influenced the improvement of survival rate after CA.