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 (T₂) and 24 h (T₂₄) of reperfusion. Sham-operated, non-clamped animals (T₀) served as controls in both groups. Renal function, kidney morphology and interleukin 1β (IL-1β), 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-1β was lower at T₀, while IL-6 at T₂ was lower in G_DHEA than in G_PG.While renal VEGF mRNA expression remained unchanged, protein levels were increased at T₂ and T₂₄compared to T₀ kidneys in both groups. VEGF protein levels were lower at T₂ and T₂₄in G_DHEA than in G_PG. Conclusion: We found that DHEA pretreatment alters renal IL-1β, 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.