INFLUENCE OF THE 21-AMINOSTEROID U74389F ON ISCHEMIA-REPERFUSION INJURY IN THE RAT

We examined the effects of the administration of 1-piperazinyl]-pregna -1,4-9(11)-triene-3,20-dione, monomethansulfonate (U74389F), a 21-amin osteroid and so-called lazaroid, that is characterized by an inhibitor y activity against iron-dependent lipid peroxidation, on ischemia-repe rfusion renal injury in a rat model. After either 60 or 90 min of isch emia, plus 2 or 24 h of reperfusion, kidneys were assayed for glutathi one, adenine nucleotides and lipid peroxidation products. 60 min of is chemia produced too little oxidative stress and/or too much spontaneou s recovery to allow visualization of the protective effect of the drug . 90 min of ischemia followed by reperfusion induced significant gluta thione oxidation, the free oxidized glutathione to total glutathione r edox ratio (%) being enhanced from 4.6 +/- 0.7% before kidney clamping to 11 +/- 1 and 8.6 +/- 1.4% at 2 and 24 h reperfusion, respectively. Treatment with the lazaroid provided significant protection against t his oxidation (4.9 +/- 1.05% at 24 h reperfusion). Results of lipid pe roxidation confirmed the antioxidant effect of the lazaroid. In conclu sion this study provides evidence for a protective role of the tested lazaroid against ischemia-reperfusion renal injury in the rat.