Dehydroepiandrosterone Pretreatment Alters the Ischaemia/Reperfusion-Induced VEGF, IL-1 and IL-6 Gene Expression in Acute Renal Failure

Abstract

Background: Beneficial effects of dehydroepiandrosterone (DHEA) pretreatment were reported in ischaemia/reperfusion (I/R)-induced kidney damage. Methods: To investigate the mechanism of DHEA pretreatment during renal I/R injury, the left renal pedicles of DHEA- [G(DHEA); 4.0 mg/kg/day DHEA dissolved in propylene glycol (PG)] and PG-pretreated male Wistar rats (G(PG)) were clamped for 55 min followed by 2 (T-2) and 24 h (T-24) of reperfusion. Sham-operated, non-clamped animals (T-0) served as controls in both groups. Renal function, kidney morphology and interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) expression were determined in the kidneys of both groups. Results: Renal functional parameters and kidney structure did not differ in G(DHEA) versus G(PG) at any time point. Renal mRNA expression of IL-1 beta was lower at T-0, while IL-6 at T-2 was lower in G(DHEA) than in G(PG). While renal VEGF mRNA expression remained unchanged, protein levels were increased at T-2 and T-24 compared to T-0 kidneys in both groups. VEGF protein levels were lower at T-2 and T-24 in G DHEA than in GPG. Conclusion: We found that DHEA pretreatment alters renal IL-1 beta, IL-6 and VEGF synthesis. Moreover, contrary changes in VEGF mRNA and protein levels suggest that VEGF synthesis - distinct from other organs - might be primarily posttranscriptionally regulated in postischaemic rat kidneys. Copyright (C) 2009 S. Karger AG, Basel