Effect of a novel nuclear factor-κB activation inhibitor on renal ischemia-reperfusion injury.

Abstract

BACKGROUND: In kidney transplantation, the relationship between prolonged warm or cold ischemic storage of kidneys and a higher incidence of delayed graft function is previously known, and delayed graft function has been known to aggravate poor long-term graft survival. We investigated the effect of a novel nuclear factor-κB activation inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on renal ischemia-reperfusion (I/R) injury. METHODS: DHMEQ was administered to Lewis rats once just before renal artery clamping (DHMEQ pretreatment group), and the effect on I/R injury was investigated. RESULTS: In the DHMEQ pretreatment group, the 24-hr urine volume on days 1 to 3 after I/R was significantly larger, and the protein concentration of the urine on days 2 to 7 was significantly smaller than in the untreated group. The serum creatinine level was significantly improved, and significantly lower levels of the inflammatory cells and inflammatory cytokines were present in the kidneys on day 1. The relative ratio of nuclear to cytoplasmic nuclear factor-κB and oxidative stress of kidney tissue on day 1 were significantly decreased. CONCLUSIONS: Treatment with DHMEQ before renal artery clamping may therefore be useful for renal I/R injury and application to renal transplantation is expected.