Dehydroepiandrosterone pretreatment alters the ischaemia/reperfusion-induced VEGF, IL-1 and IL-6 gene expression in acute renal failure.
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 1beta (IL-1beta), 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-1beta 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 G(PG).


CONCLUSIONS
We found that DHEA pretreatment alters renal IL-1beta, 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.
Vannay
Adám
A
Research Laboratory of Paediatrics and Nephrology, Hungarian Academy of Sciences, Budapest, Hungary. vannay@gyer1.sote.hu
Fekete
Andrea
A
Langer
Róbert
R
Tóth
Tibor
T
Sziksz
Erna
E
Vásárhelyi
Barna
B
Szabó
Attila J
AJ
Losonczy
Gyorgy
G
Adori
Csaba
C
Gál
Anikó
A
Tulassay
Tivadar
T
Szabó
András
A
D058186:Acute Kidney Injury / Q000150:complications*; D000818:Animals; D003687:Dehydroepiandrosterone / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D011292:Premedication / Q000379:methods*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D003687:Dehydroepiandrosterone