Thromboxane receptor signalling in renal ischemia reperfusion injury.

M.G. Snoeijs, P.E.R. Hoogland, B.T.C. Boonen, T.M. Coffman, C.J. Peutz-Kootstra, W.A. Buurman, L.W.E. van Heurn

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Abstract F(2)-isoprostanes are formed by oxidative modification of arachidonic acid and are the gold standard for detection of oxidative stress in vivo. F(2)-isoprostanes are biologically active compounds that signal through the thromboxane A(2) (TP) receptor; infusion of F(2)-isoprostanes reduces glomerular filtration in the kidney by constricting afferent arterioles. This study investigated whether endogenous F(2)-isoprostanes contribute to the pathogenesis of ischemic acute kidney injury, which is associated with oxidative stress and reduced glomerular filtration. TP receptor knockout mice-that lack F(2)-isoprostanes and thromboxane A(2) signalling-and wild-type control mice underwent 30 min of renal ischemia and 24 h of reperfusion. Kidney dysfunction, histological injury and the number of infiltrated neutrophils were similar between the two mouse strains, whereas TP receptor knockout mice had significantly more apoptotic cells and tissue lipid peroxidation than their wild-type counterparts. F(2)-isoprostanes and thromboxane B(2) were readily detectable in urine collections after surgery. The findings indicate that F(2)-isoprostanes and thromboxane A(2) signalling do not contribute critically to the pathogenesis of ischemic acute kidney injury and more generally provide evidence against a prominent role for F(2)-isoprostanes signalling in exacerbating acute disease states associated with oxidative stress.
Original languageEnglish
Pages (from-to)699-706
Number of pages8
JournalFree Radical Research
Volume45
Issue number6
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Acute kidney injury
  • F(2)-isoprostanes
  • ischemia reperfusion injury
  • thromboxane A(2)
  • TP receptor
  • III 8-ISO-PROSTAGLANDIN F2-ALPHA
  • OXYGEN FREE-RADICALS
  • IN-VIVO
  • OXIDATIVE STRESS
  • A(2) RECEPTOR
  • HUMAN KIDNEY
  • FAILURE
  • PROSTAGLANDIN
  • RESPONSES
  • MICE

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