Indomethacin attenuation of hepatic perfusion and plasma 6-ketoPGF1 alpha elevations following glutathione depletion in rabbits.
Indomethacin attenuation of hepatic perfusion and plasma 6-ketoPGF1 alpha elevations following glutathione depletion in rabbits.
复制标题
家兔谷胱甘肽耗尽后，吲哚美辛会减弱肝灌注，并导致血浆 6-ketoPGF1 α 升高。
DOI：
10.1016/0304-4165(91)90198-p
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Holmes,KR
中科院分区：
文献类型：
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作者：
Bottje,W;Glahn,R;Beers,K;Nejad,H;Graupner,W;Holmes,KR
谷胱甘肽 (GSH) 对于解毒和调节环氧合酶活性很重要。由于肝脏含有高水平的 GSH，异生素引起的肝脏 GSH 变化可能会通过改变前列腺素合成来影响肝组织血液灌注 (HP)。在麻醉的雄性新西兰兔中，用 GSH 单乙酯升高 GSH 对 HP 没有影响。用马来酸二乙酯治疗兔子以消耗谷胱甘肽，对之前服用谷胱甘肽单乙酯的动物的 HP 也没有影响。然而，在用谷胱甘肽单乙酯处理之前，先用马来酸二乙酯处理的兔子，HP 在 20 分钟内增加。在另一项实验中，GSH 消耗后 HP 也出现类似的升高，同时动脉血浆 6-ketoPGF1α（前列环素的稳定代谢物）水平比对照组高 4 倍。马来酸二乙酯后血浆 TxB2（凝血烷的稳定代谢物）也有所增加，但仅达到比 6-ketoPGF1α 低 25 倍的水平。由于吲哚美辛阻止 HP 的升高以及 6-ketoPGF1α 和 TxB2 的增加，因此这些结果表明，由于一种或多种花生四烯酸代谢物的合成增加，GSH 耗尽后可能会出现 HP 的变化，并暗示前列环素可能是这种现象的介质。
Glutathione (GSH) is important in detoxification and regulating cyclooxygenase activity. Since the liver has high levels of GSH, xenobiotic-induced changes in hepatic GSH could affect hepatic tissue blood perfusion (HP) via alterations in prostaglandin synthesis. In anesthetized male New Zealand rabbits, elevating GSH with GSH monoethyl ester had no affect on HP. Treatment of rabbits with diethyl maleate to deplete GSH also had no affect on HP in animals previously given GSH monoethyl ester. However, HP increased within 20 min in rabbits treated with diethyl maleate prior to GSH monoethyl ester. In another experiment, a similar rise in HP following GSH depletion was accompanied by arterial plasma 6-ketoPGF1α(the stable metabolite of prostacyclin) levels that were 4-times higher than in the controls. Plasma TxB2(the stable metabolite of throm☐ane) also increased following diethyl maleate, but only to levels that were 25-times lower than for 6-ketoPGF1α. Since indomethacin blocked the rise in HP, as well as the increases in 6-ketoPGF1αand TxB2, these results indicate changes in HP may occur following GSH depletion as a result of increased synthesis of one or more arachidonic acid metabolites and implicate prostacyclin as a possible mediator of this phenomenon.