Effect Of Curcumin On Renal Injury Of Rats Underwent Cardiopulmonary Bypass

Acute renal insufficiency (ARI) is a frequent complication after cardiac surgery withcardiopulmonary bypass (CPB). Although heart surgery, cardiopulmonary bypass techniqueand postoperative intensive care levels have been improved, renal oxidative stress andinflammation reaction are still obvious because of organ ischemia and reperfusion, contacts ofblood and exoteric pipages, etc. Those reactions cause damage to the kidneys and make theARI occurrence rate up to30%, which greatly increased the mortality of patients, especiallypatients needing hemodialysis. So, it is valuable to find a right medication for renal injury ofpatients after CPB.Nuclear factor κB (NF-κB) signaling pathway was widely recognized as an importantregulate process for pro-inflammatory cytokines that promote the inflammatory response, andit also plays a regulatory role in oxidative stress due to regulation for some oxygen freeradicals. While the activation and regulation of transcription of NF-κB is undoubtedly the keyto the whole signaling pathway. Therefore, the drug will weaken oxidative stress andinflammatory reaction, protect organs and even the whole body if it has the ability to inhibitthe activation and regulation of NF-κB.Currently, many researchers have proven that curcumin has the capability to makeanti-inflammatory, antioxidant and other pharmacological effects, but there is no paper reportsthe effects of curcumin on oxidative stress and inflammatory reaction post-CPB by now. Weaimed to determine whether curcumin could weaken renal damage by the rat CPB model andcurcumin pretreatment, and to investigate the potential mechanism of this drug in this study,which will provide a theoretical basis and data reference for further research of the relevantcontent, and experimental basis for look for a clinical renal protective agent. Part One Effect of Curcumin on Renal Oxidative StressInjury after Cardiopulmonary BypassObjectiveThe aim is to identify the effects and potential mechanisms of curcumin on renaloxidative stress injury in rats under CPB.MethodsMale Sprague-Dawley rats (400500g) were divided into four groups randomly (n=10per group): control, model, vehicle, and curcumin groups. Among that model, vehicle, andcurcumin groups suffered CPB operation, and control group were operated just as modelgroup except vessels intubation and CPB. All rats were administered sodium chloride or drugby intraperitoneal injection2h before operation. Kidney tissues were harvested12h afteroperation for histological examination and determination of superoxide dismutase (SOD),malonaldehyde (MDA), reduced glutathione hormone (GSH) and NF-κB.ResultsThe contents of MDA and activation of NF-κB in model and curcumin groups weresignificantly higher than the control group (P<0.05), and curcumin group were lower thanmodel group obviously (P<0.05). Besides, compared with control group, model and curcumingroups markedly decreased SOD and GSH concentrations (P<0.05), but curcumin group hadhigher levels of SOD and GSH than model group. Histopathologic findings of model groupconfirmed that there were renal impairments characterized by tubular epithelial cell dilatationand vacuole formation, but impairments of curcumin group were relatively small. The scoreof model group was significantly higher than of curcumin group (P<0.05). There were notsignificantly different between vehicle and model groups in all detection results (P>0.05).ConclusionCurcumin is effective in preventing CPB-induced renal oxidative stress injury probablythrough inhibiting the production of oxyradicals, and promoting the generation ofantioxidases. Part Two Effect of Curcumin on Renal Inflammatory Injury afterCardiopulmonary BypassObjectiveThe aim is to identify the effects and potential mechanisms of curcumin on renalinflammatory damage in rats under CPB.MethodsMale Sprague-Dawley rats (400500g) were divided into five groups randomly (n=10per group): control, model, vehicle, low-dose curcumin and high-dose curcumin groups.Among that the last four groups suffered CPB operation, and the control group were operatedjust as model group except vessels intubation and CPB. All rats were administered sodiumchloride or drug by intraperitoneal injection2h before operation. Blood samples werecollected before CPB, at the termination of CPB，and at2,4,12,24h after CPB for detectionof serum creatinine, cystatin C and tumor necrosis factor α (TNF-α). Kidney tissues wereharvested24h after CPB for determining TNF-α, cyclooxygenase-2(COX-2) and NF-κB.ResultsCompared with model group, low-dose and high-dose curcumin groups markedlyattenuated creatinine, cystatin C, and TNF-α concentrations in serum at2,4,12,24h afterCPB, and COX-2, TNF-α, and NF-κB levels in tissues(P<0.05), however all the three groupshave higher concentrations than the control group(P<0.05). Histopathologic findings of modelgroup confirmed that there were renal impairments characterized by tubular dilatation，vacuole formation, and stroma bleeding, but impairments of low-dose and high-dosecurcumin groups were relatively small. The score of model group was significantly higherthan of both curcumin groups (P<0.05). There were not significantly different betweenvehicle and model groups in all detection results (P>0.05).ConclusionCurcumin is effective in preventing CPB-induced renal inflammatory damage probablythrough inhibiting the activation of NF-κB, as well as the cytokines secretion. Therefore,curcumin may be regard as a potent protectant for kidneys after CPB.