PROTECTION FROM RENAL ISCHEMIA-REPERFUSION INJURY BY THE 2-METHYLAMINOCHROMAN U83836E

Background. In a prior study the 21-aminosteroid (lazaroid) U74389F pr ovided in vivo protection from oxidative stress when used as a prevent ive therapy in ischemia-reperfusion injury in the kidney. As the cell membrane is the principal site for lipoperoxidation, in the current st udy the very lipophilic 2-methylaminochroman U83836E, a recently devel oped lazaroid, was administered to rats at 3 mg/kg before renal ischem ia-reperfusion. In addition to the biochemical parameters, the renal f unction and the histological appearance were carefully evaluated. Meth ods. Glutathione, adenine nucleotides and lipid peroxidation products were determined in kidneys reperfused for 2 and 24 hours after 90 minu tes of ischemia. Renal function was assessed by plasma creatinine, and renal injury by histological examination. Results. Reperfusion-induce d glutathione oxidation, expressed as an oxidized-to-total glutathione ratio, was significantly attenuated both after 2 and 24 hours of repe rfusion by treatment with U83836E. Adenosine triphosphate (ATP) was st ill significantly depleted after 24 hours in the control group, while at the same time treated animals had already recovered to baseline val ues. Lipid peroxidation products were significantly lower in lazaroid- groups both after 2 and 24 hours of reperfusion. Renal function after 24 hours of reperfusion was notably better in the treated rats. Histol ogical examination confirmed the protective action of the drug. After 24 hours the control group showed large areas of parenchymal hemorrhag e and necrosis with dilated tubules and blood vessel thrombosis, while treated animals showed small necrotic areas with a background of mild interstitial inflammatory cells. Conclusions. Our results suggest tha t there is a protective effect of U83836E in ischemia-reperfusion inju ry, in that tissue damage due to oxidative stress is reduced, thus ame liorating renal function impairment.