Torres A M, Rodriguez J V, Elías M M
Departamento de Morfologia, Fisiologia y Farmacoloigia, Facultad de Ciencias Bioquimicas y Farmaceuticas, Conicet-Universidad Nacional de Rosario, Argentina.
J Pharmacol Exp Ther. 1989 Jul;250(1):247-53.
Previous works supported the idea that the thick ascending limb of Henle was the target structure for glutathione (GSH) depletion effects. In order to obtain more evidence on this hypothesis, we compared GSH depletion effects with those of two loop diuretics: furosemide and ethacrynic acid. The submaximal tubular effects observed with furosemide were magnified when the kidneys were previously GSH depleted, but maximal tubular effects of furosemide were GSH independent. This last observation suggested that furosemide and GSH depletion have common sites or mechanisms of action. On the other hand, ethacrynic acid tubular effects were always magnified when the rats were GSH depleted. As it has been proposed that the renal actions of furosemide and ethacrynic acid are at least in part mediated by prostaglandins, another set of experiments was performed using indomethacin to examine the possible role of renal prostaglandins in GSH depletion effects. It was observed that indomethacin greatly improved tubular functions in GSH-depleted rats suggesting that an increase in prostaglandins levels should be involved in the renal defects observed during GSH depletion. All these data give additional support to the idea that the thick ascending limb cells may have a special sensitivity to the effects of GSH depletion probably mediated by prostaglandins.
先前的研究支持这样一种观点，即髓袢升支粗段是谷胱甘肽（GSH）耗竭效应的靶结构。为了获得更多关于这一假说的证据，我们将GSH耗竭效应与两种袢利尿剂（呋塞米和依他尼酸）的效应进行了比较。当肾脏先前已出现GSH耗竭时，呋塞米观察到的次最大肾小管效应会放大，但呋塞米的最大肾小管效应与GSH无关。这最后一项观察结果表明，呋塞米和GSH耗竭具有共同的作用位点或机制。另一方面，当大鼠出现GSH耗竭时，依他尼酸的肾小管效应总是会放大。由于有人提出呋塞米和依他尼酸的肾脏作用至少部分是由前列腺素介导的，因此使用吲哚美辛进行了另一组实验，以研究肾脏前列腺素在GSH耗竭效应中的可能作用。观察到吲哚美辛可显著改善GSH耗竭大鼠的肾小管功能，这表明前列腺素水平升高应与GSH耗竭期间观察到的肾脏缺陷有关。所有这些数据进一步支持了这样一种观点，即髓袢升支粗段细胞可能对可能由前列腺素介导的GSH耗竭效应具有特殊敏感性。
