Influence of the 21-aminosteroid U74389F on ischemia-reperfusion injury in the rat

Rita Paroni, Elena De Vecchi, Lorenzo Lubatti, Elena Conti, Claudio Beretta, Paola Rinaldi, Marzia Galli Kienle, Rinaldo Trazzi

Research output: Contribution to journalArticlepeer-review

Abstract

We examined the effects of the administration of 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-pregna-1,4,9(11)-triene-3,20-dione, monomethansulfonate (U74389F), a 21-aminosteroid and so-called lazaroid, that is characterized by an inhibitory activity against iron-dependent lipid peroxidation, on ischemia-reperfusion renal injury in a rat model. After either 60 or 90 min of ischemia, plus 2 or 24 h of reperfusion, kidneys were assayed for glutathione, adenine nucleotides and lipid peroxidation products. 60 min of ischemia produced too little oxidative stress and/or too much spontaneous recovery to allow visualization of the protective effect of the drug. 90 min of ischemia followed by reperfusion induced significant glutathione oxidation, the free oxidized glutathione to total glutathione redox 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 this oxidation (4.9 ± 1.05% at 24 h reperfusion). Results of lipid peroxidation confirmed the antioxidant effect of the lazaroid. In conclusion this study provides evidence for a protective role of the tested lazaroid against ischemia-reperfusion renal injury in the rat.

Original languageEnglish
Pages (from-to)737-742
Number of pages6
JournalEuropean Journal of Pharmacology
Volume294
Issue number2-3
DOIs
Publication statusPublished - Dec 29 1995

Keywords

  • 21-Aminosteroid
  • Glutathione
  • Ischemia-reperfusion injury
  • Kidney, rat
  • Lipid peroxidation
  • Oxidative stress

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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