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Inhibition of 20-HETE synthesis and action protects the kidney from ischemia/reperfusion injury

Item Type:Article
Title:Inhibition of 20-HETE synthesis and action protects the kidney from ischemia/reperfusion injury
Creators Name:Hoff, U. and Lukitsch, I. and Chaykovska, L. and Ladwig, M. and Arnold, C. and Manthati, V.L. and Fuller, T.F. and Schneider, W. and Gollasch, M. and Mueller, D.N. and Flemming, B. and Seeliger, E. and Luft, F.C. and Falck, J.R. and Dragun, D. and Schunck, W.H.
Abstract:20-Hydroxyeicosatetraenoic acid (20-HETE) production is increased in ischemic kidney tissue and may contribute to ischemia/reperfusion (I/R) injury by mediating vasoconstriction and inflammation. To test this hypothesis, uninephrectomized male Lewis rats were exposed to warm ischemia following pretreatment with either an inhibitor of 20-HETE synthesis (HET0016), an antagonist (20-hydroxyeicosa-6(Z),15(Z)-dienoic acid), an agonist (20-hydroxyeicosa-5(Z),14(Z)-dienoic acid), or vehicle via the renal artery and the kidneys were examined 2 days after reperfusion. Pretreatment with either the inhibitor or the antagonist attenuated I/R-induced renal dysfunction as shown by improved creatinine clearance and decreased plasma urea levels, compared to controls. The inhibitor and antagonist also markedly reduced tubular lesion scores, inflammatory cell infiltration, and tubular epithelial cell apoptosis. Administering the antagonist accelerated the recovery of medullary perfusion, as well as renal medullary and cortical re-oxygenation, during the early reperfusion phase. In contrast, the agonist did not improve renal injury and reversed the beneficial effect of the inhibitor. Thus, 20-HETE generation and its action mediated kidney injury due to I/R. Whether or not these effects are clinically important will need to be tested in appropriate human studies.
Keywords:Acute Kidney Injury, Eicosanoids, Ischemia / Reperfusion, Animals, Rats
Source:Kidney International
ISSN:0085-2538
Publisher:Nature Publishing Group (U.S.A.)
Volume:79
Number:1
Page Range:57-65
Date:January 2011
Official Publication:https://doi.org/10.1038/ki.2010.377
PubMed:View item in PubMed

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