Protective mechanisms of piperine against renal ischemia–reperfusion injury in rats

摘要

Background: Renalischemia–reperfusion injury (IRI) isa majorclinical problemassociated with kidney transplantation, leading to highmortality and morbidity. IRI involvesactivation of oxidativestressand inflammatory pathways,eventually leading to cell death and organ failure. Piperineisa phenolicactiveingredient of black pepper, which showed promising antioxidantand anti-inflammatory potential. Objectives: We hypothesized that piperine would protectagainst renalIRI in rats via inhibition of oxidativestressand inflammation. Materials andMethods: Male Sprague Dawley rats weresubdivided into four groups;sham, IR, IR piperine,and sham piperine. Allanimals have been treated for 4 days with either vehicle or piperine(100 mg/kg/day). One hourafter thelast piperine or vehicleadministration, animals weresubjected to bilateralrenalischemiafor 45 min by clamping both renal pedicles, followed by reperfusion for 24 h. At theend oftheexperiments, kidneys were harvested for the determination oflipid peroxidation (malondialdehyde[MDA]), reduced glutathione(GSH), inflammatory and apoptotic markers,and histopathology. Serumlevels ofcreatinineand urea have been determined. Results: Induction ofrenalIRincreased renal oxidativestress (increased MDAand decreased GSH)and theexpression levels ofinflammatory and proapoptotic genes (nuclear factor-kappa B, inducible nitric oxidesynthase,cyclooxygenase-2,and caspase-3). Moreover, serumlevels ofcreatinineand urea weresignificantly elevated. Alternatively, pretreatment oftheanimals with piperineresulted in normalization ofthese parameters. Conclusion: Theresults showed that piperine pretreatment protectsagainst IRI in rat kidneys via mechanisms involving amelioration of oxidative stressalongwith inflammatory and apoptotic pathways.