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Transplant Proc. 2013 Mar;45(2):517-22. doi: 10.1016/j.transproceed.2012.02.051.

Renoprotective role of fenoldopam pretreatment through hypoxia-inducible factor-1alpha and heme oxygenase-1 expressions in rat kidney transplantation.

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1
Department of Urology, Xijing Hospital, Xi'an, Shaanxi, China.

Abstract

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

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