TY - JOUR
T1 - Influence of the 21-aminosteroid U74389F on ischemia-reperfusion injury in the rat
AU - Paroni, Rita
AU - De Vecchi, Elena
AU - Lubatti, Lorenzo
AU - Conti, Elena
AU - Beretta, Claudio
AU - Rinaldi, Paola
AU - Kienle, Marzia Galli
AU - Trazzi, Rinaldo
PY - 1995/12/29
Y1 - 1995/12/29
N2 - 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.
AB - 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.
KW - 21-Aminosteroid
KW - Glutathione
KW - Ischemia-reperfusion injury
KW - Kidney, rat
KW - Lipid peroxidation
KW - Oxidative stress
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U2 - 10.1016/0014-2999(95)00638-9
DO - 10.1016/0014-2999(95)00638-9
M3 - Article
C2 - 8750740
AN - SCOPUS:0029609314
VL - 294
SP - 737
EP - 742
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2-3
ER -