RESUMO
The detrimental role of oxidative stress has been widely described in tissue damage caused by ischemia-reperfusion. A nonenzymatic, reactive oxygen species-related pathway has been suggested to produce 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)), an epimer of prostaglandin F(2alpha) (PGF(2alpha)), which has been proposed as an indicator of oxidative stress. Using an in vivo ischemia-reperfusion model in rat kidneys, we investigated intrarenal accumulation of 8-iso-PGF(2alpha) and PGF(2alpha). Both prostanoids accumulated in the ischemic kidney and disappeared upon reperfusion. In addition, a nonselective (acetylsalicylic acid) or selective cyclooxygenase (COX) 1 inhibitor (SC-560) completely abrogated the 8-iso-PGF(2alpha) and PGF(2alpha) formation in kidneys subjected to ischemia. COX2 inhibition had no effect on the production of these prostanoids. Therefore the two metabolites of arachidonic acid seemed to be produced via an enzymatic COX1-dependent pathway. Neither COX overexpression nor COX activation was detected. We also investigated renal glutathione, which is considered to be the major thiol-disulfide redox buffer of the tissue. Total and oxidized glutathione was decreased during the ischemic period, whereas no further decrease was seen for up to 60 min of reperfusion. These data demonstrate that a dramatic decrease in antioxidant defense was initiated during warm renal ischemia, whereas the 8-iso-PGF(2alpha) was related only to arachidonate conversion by COX1.
Assuntos
F2-Isoprostanos/química , Isoenzimas/metabolismo , Rim/patologia , Oxirredução , Prostaglandina-Endoperóxido Sintases/metabolismo , Traumatismo por Reperfusão , Animais , Ácido Araquidônico/metabolismo , Ciclo-Oxigenase 1 , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Inibidores Enzimáticos/farmacologia , Radicais Livres , Cromatografia Gasosa-Espectrometria de Massas , Glutationa/metabolismo , Isquemia , Rim/metabolismo , Cinética , Masculino , Proteínas de Membrana , Estresse Oxidativo , Pirazóis/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
Ischemia-reperfusion injury (IRI) is associated with an increased risk of acute rejection, delayed graft function, or chronic graft dysfunction. Mitochondria plays a central role in this process. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na(+) version of UW (HEH) or Celsior (CEL) a newly developed high-Na(+) solution, with or without trimetazidine (TMZ). Kidney function was better preserved in HEH after 24 hr and particularly 48- and 72-hr cold storage than in CEL and UW. TMZ improved the preservation quality when added to the different solutions tested, particularly after 48- and 72-hr cold storage. Interstitial fibrosis and tubular atrophy were reduced in HEH with TMZ. CD4(+) T-cell infiltration was also modulated by the preservation conditions. Peripheral-type benzodiazepine receptor (PBR) positive cells infiltration was also modulated by preservation conditions. TMZ was efficient to reduce IRI when added in the various preservation solutions. These results suggest that protection of the mitochondrial function should be a major target to limit IRI. In addition, this study outlines the role of CD4(+) T cells and PBR expression in inflammatory responses after IRI.