P23 Pharmacological induction of CBS-mediated H2S production attenuates renal damage following deep hypothermia and rewarming

Abstract

Hypothermic static preservation is commonly applied to preserve organ grafts during transplantation. However, cold ischemia is associated with the induction of renal injury, in which reactive oxygen species (ROS) play a major role. We recently reported that cellular uptake of catecholamines prevents hypothermia/rewarming-induced cell death by inhibiting ROS production. We also showed in cultured rat smooth muscle aortic cells that administration of catecholamines such as dopamine boosts endogenous H 2 S production leading to cell survival under hypothermic condition. Therefore in this study, we investigated whether these mechanisms are operational in vivo in the rat kidney, by investigating the effect of dopamine on renal injury induced by hypothermia and rewarming under ketamine anesthesia. Our results show that forced hypothermia followed by rewarming of rats induces glomerular and interstitial injury in animals anesthetized with ketamine, as indicated by histopathological changes, higher KIM-1 expression, influx of neutrophils and macrophages, and high ROS generation. Addition of dopamine on the other hand, reduced renal hypothermia/rewarming injury in animals anesthetized with ketamine and upregulated CBS expression and subsequent H 2 S production. These demonstrate that dopamine has renoprotection via CBS-induced H 2 S production against organ damage induced by hypothermia/rewarming.