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对苯二甲酸的肾脏处理

The renal handling of terephthalic acid.

作者信息

Tremaine L M, Quebbemann A J

出版信息

Toxicol Appl Pharmacol. 1985 Jan;77(1):165-74. doi: 10.1016/0041-008x(85)90277-7.

Abstract

By use of the Sperber in vivo chicken preparation method (1948, Ann. R. Agric. Coll. Swed. 15, 317-349), infusion of radiolabeled terephthalic acid ([14C]TPA) into the renal portal circulation revealed a first-pass excretion of the unchanged compound into the urine. This model was utilized further to characterize the excretory transport of [14C]TPA and provide information on the structural specificity in the secretion of dicarboxylic acids. At an infusion rate of 0.4 nmol/min. 60% of the [14C]TPA which reached the kidney was directly excreted. An infusion rate of 3 or 6 mumol/min resulted in complete removal of [14C]TPA by the kidney. These results indicate that TPA is both actively secreted and actively reabsorbed when infused at 0.4 nmol/min and that active reabsorption is saturated with the infusion of TPA at higher concentrations. The secretory process was saturated with the infusion of TPA at 40 mumol/mn. The excretory transport of TPA was inhibited by the infusion of probenecid, salicylate, and m-hydroxybenzoic acid, indicating that these organic acids share the same organic anion excretory transport process. m-Hydroxybenzoic acid did not alter the simultaneously measured excretory transport of p-aminohippuric acid (PAH), suggesting that there are different systems involved in the secretion of TPA and PAH. The structural specificity for renal secretion of dicarboxylic acids was revealed by the use of o-phthalic acid and m-phthalic acid as possible inhibitors of TPA secretion. m-Phthalate, but not o-phthalate, inhibited TPA excretory transport, indicating that there is some specificity in the renal secretion of carboxy-substituted benzoic acids. TPA was actively accumulated by rat and human cadaver renal cortical slices.

摘要

采用斯珀伯(Sperber)体内鸡制备方法(1948年,《瑞典皇家农业学院学报》15卷,第317 - 349页),将放射性标记的对苯二甲酸([¹⁴C]TPA)注入肾门静脉循环,结果显示未变化的化合物首次通过尿液排泄。该模型被进一步用于表征[¹⁴C]TPA的排泄转运,并提供有关二羧酸分泌中结构特异性的信息。以0.4 nmol/分钟的输注速率,到达肾脏的[¹⁴C]TPA中有60%直接排泄。3或6 μmol/分钟的输注速率导致肾脏完全清除[¹⁴C]TPA。这些结果表明,以0.4 nmol/分钟输注时,TPA既被主动分泌又被主动重吸收,并且在较高浓度输注TPA时主动重吸收达到饱和。在40 μmol/分钟输注TPA时,分泌过程达到饱和。丙磺舒、水杨酸盐和间羟基苯甲酸的输注抑制了TPA的排泄转运,表明这些有机酸共享相同的有机阴离子排泄转运过程。间羟基苯甲酸未改变同时测量的对氨基马尿酸(PAH)的排泄转运,这表明TPA和PAH的分泌涉及不同的系统。通过使用邻苯二甲酸和间苯二甲酸作为TPA分泌的可能抑制剂,揭示了二羧酸肾脏分泌的结构特异性。间苯二甲酸盐而非邻苯二甲酸盐抑制了TPA的排泄转运,表明在羧基取代苯甲酸的肾脏分泌中存在一定的特异性。TPA被大鼠和人尸体肾皮质切片主动积累。

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