Mølck A M, Friis C
Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, Frederiksberg, Denmark.
Pharmacol Toxicol. 1998 Nov;83(5):208-13. doi: 10.1111/j.1600-0773.1998.tb01470.x.
Paraquat is a non-selective herbicide, which induces lung, liver and kidney damage in mammalian species. Because paraquat is mainly eliminated by the kidneys, the induced kidney damage may suppress excretion and enhance toxicity of paraquat in other organs. Since proximal tubules appear to be the target segment of the nephron, this study focuses on transport of paraquat by isolated proximal tubular segments from rabbits. Proximal tubules were isolated using a combined magnetic iron perfusion and collagenase method. Incubations were carried out at 25 degrees under 100% oxygen or nitrogen for varying times at different concentrations of paraquat. Proximal tubules accumulated paraquat by a slow process, which was non-saturable in the concentration range (0.1-5 microM) examined. Tubular excretion of cations involves transport across both basolateral and luminal membranes of the cell. The basolateral uptake of paraquat was inhibited by low temperature, low medium pH and quinine. In contrast to quinine, tetraethylammonium enhanced paraquat accumulation probably by trans-stimulating the basolateral uptake. Incubation under nitrogen enhanced paraquat accumulation possibly by reducing the transport out of the cell at the luminal membrane. Thus, this study shows that proximal tubules accumulate paraquat by an active process related to the cation transport mechanism.
百草枯是一种非选择性除草剂，可在哺乳动物物种中引起肺、肝和肾损伤。由于百草枯主要通过肾脏排出，因此所诱导的肾损伤可能会抑制其排泄，并增强百草枯在其他器官中的毒性。由于近端小管似乎是肾单位的靶节段，本研究聚焦于从兔分离的近端小管节段对百草枯的转运。采用磁铁灌注和胶原酶联合方法分离近端小管。在25摄氏度下，于100%氧气或氮气环境中，以不同浓度的百草枯进行不同时间的孵育。近端小管通过一个缓慢的过程积累百草枯，在所检测的浓度范围（0.1 - 5微摩尔）内该过程不饱和。阳离子的肾小管排泄涉及跨细胞基底外侧膜和管腔膜的转运。低温、低培养基pH值和奎宁可抑制百草枯的基底外侧摄取。与奎宁相反，四乙铵可能通过反刺激基底外侧摄取来增强百草枯的积累。在氮气环境下孵育可能通过减少管腔膜处细胞对其的转运来增强百草枯的积累。因此，本研究表明近端小管通过与阳离子转运机制相关的主动过程积累百草枯。
