sch-23390 and Reperfusion-Injury

Donor preconditioning by fenoldopam is demonstrated to improve graft function in recipients. Involvement of hypoxia-inducible factor-1alpha (HIF-1α) and heme oxygenase-1 (HO-1) in renoprotection after fenoldopam pretreatment was investigated.. Donor Sprague-Dawley (SD) rats were intravenously treated with fenoldopam (5 μg/kg · min), Sch23390 (10 μg/kg · min), or fenoldopam + Sch23390 for 1 hour. Kidneys experiencing 24 hours of cold preservation were transplanted into syngeneic SD recipients. Ten days after transplantion, serum concentrations of creatinine (sCR), blood urea nitrogen (BUN), interleukin (IL)-8, and tumor necrosis factor (TNF)-α in recipient were determined. Grafts were procured for histopathological examination, apoptosis analysis, and measurements of malondialdehyde and total superoxide dismutase activities; meanwhile, both protein level and mRNA level of HIF-1α and HO-1 were assessed.. Fenoldopam preconditioning significantly decreased the serum concentrations of sCR, BUN, IL-8, and TNF-α in recipients. Low apoptosis rate and reduced oxidative stress were found in these grafts. Increased HIF-1α activation and HO-1 expression were observed in fenoldopam pretreatment group. Sch23390 partly inhibited the effects of fenoldopam in the combination group.. Donor preconditioning by fenoldopam exerts renoprotection in grafts, at least in part, through HIF-1α activation and HO-1 expression. This provides a preference for further studies.

Topics: Animals; Apoptosis; Benzazepines; Blood Urea Nitrogen; Cold Ischemia; Creatinine; Cytoprotection; Disease Models, Animal; Fenoldopam; Heme Oxygenase (Decyclizing); Hypoxia-Inducible Factor 1, alpha Subunit; Infusions, Intravenous; Interleukin-8; Kidney; Kidney Transplantation; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; RNA, Messenger; Superoxide Dismutase; Time Factors; Tumor Necrosis Factor-alpha