title: Thromboxane receptor signalling in renal ischemia reperfusion injury.
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.
authors: Department of Surgery, Maastricht University Medical Center, the Netherlands. m.snoeijs@mumc.nl
authors: Maarten G J
authors: MG
authors: Snoeijs
authors: Pieter R
authors: PR
authors: Hoogland
authors: Bas
authors: B
authors: Boonen
authors: Thomas M
authors: TM
authors: Coffman
authors: Carine J
authors: CJ
authors: Peutz-Kootstra
authors: Wim A
authors: WA
authors: Buurman
authors: L W Ernest
authors: LW
authors: van Heurn
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants; D001806:Blood Urea Nitrogen; D003401:Creatine / Q000097:blood; D028441:F2-Isoprostanes / Q000378:metabolism; D017353:Gene Deletion; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017482:Receptors, Thromboxane / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D028441:F2-Isoprostanes; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D003401:Creatine