Thromboxane receptor signalling in renal ischemia reperfusion injury

Abstract

F2-isoprostanes are formed by oxidative modification of arachidonic acid and are the gold standard for detection of oxidative stress in vivo. F2-isoprostanes are biologically active compounds that signal through the thromboxane A2 (TP) receptor; infusion of F2-isoprostanes reduces glomerular filtration in the kidney by constricting afferent arterioles. This study investigated whether endogenous F2-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 F2-isoprostanes and thromboxane A2 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. F2-isoprostanes and thromboxane B2 were readily detectable in urine collections after surgery. The findings indicate that F2-isoprostanes and thromboxane A2 signalling do not contribute critically to the pathogenesis of ischemic acute kidney injury and more generally provide evidence against a prominent role for F2-isoprostanes signalling in exacerbating acute disease states associated with oxidative stress.