Paroni R, De Vecchi E, Lubatti L, Conti E, Beretta C, Rinaldi P, Kienle M G, Trazzi R
Department of Laboratory Medicine, IRCCS H. San Raffaele, Milan, Italy.
Eur J Pharmacol. 1995 Dec 29;294(2-3):737-42. doi: 10.1016/0014-2999(95)00638-9.
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.
我们研究了21-[4-(2,6-二-1-吡咯烷基-4-嘧啶基)-1-哌嗪基]-孕甾-1,4,9(11)-三烯-3,20-二酮单甲磺酸盐（U74389F），一种21-氨基类固醇即所谓的类维生素E，其具有抑制铁依赖性脂质过氧化的活性，对大鼠模型缺血再灌注肾损伤的影响。在缺血60或90分钟，再加2或24小时再灌注后，检测肾脏中的谷胱甘肽、腺嘌呤核苷酸和脂质过氧化产物。60分钟的缺血产生的氧化应激过少和/或自发恢复过多，以至于无法观察到该药物的保护作用。90分钟缺血后再灌注诱导了显著的谷胱甘肽氧化，游离氧化型谷胱甘肽与总谷胱甘肽的氧化还原比率（%）从肾夹闭前的4.6±0.7%分别增加到再灌注2小时和24小时时的11±1%和8.6±1.4%。用类维生素E治疗可显著保护免受这种氧化（再灌注24小时时为4.9±1.05%）。脂质过氧化结果证实了类维生素E的抗氧化作用。总之，本研究为所测试的类维生素E对大鼠缺血再灌注肾损伤的保护作用提供了证据。
