Dinis-Oliveira R J, De Jesús Valle M J, Bastos M L, Carvalho F, Sánchez Navarro A
Department of Toxicology, University of Porto, REQUIMTE, Porto, Portugal.
Xenobiotica. 2006 Aug;36(8):724-37. doi: 10.1080/00498250600790331.
Paraquat accumulates in the lung through a characteristic polyamine uptake system. It has been previously shown that paraquat uptake can be significantly prevented if extracellular sodium (Na+) is reduced, although the available data correspond to experiments performed using tissue slices or incubated cells. This type of in vitro study fails to give information on the actual behaviour occurring in vivo since the anatomy and physiology of the studied tissue is disrupted. Accordingly, the aim of the present study was to explore the usefulness of the isolated rat lung model when applied to characterize the kinetic behaviour of paraquat in this tissue after bolus injection under standard experimental conditions as well as to evaluate the influence of iso-osmotic replacement of Na+ by lithium (Li+) in the perfusion medium. The obtained results show that the present isolated rat lung model is useful for the analysis of paraquat toxicokinetics, which is reported herein for the first time. It was also observed that Na+ depletion in the perfusion medium leads to a decreased uptake of paraquat in the isolated rat lung, although it seems that this condition does not contribute to improve the elimination of paraquat once the herbicide reaches the extravascular structures of the tissue, since the paraquat tissue wash-out phase is similar under both experimental conditions assayed.
百草枯通过一种独特的多胺摄取系统在肺中蓄积。此前已有研究表明，如果细胞外钠（Na+）减少，百草枯的摄取可被显著抑制，尽管现有数据来自使用组织切片或培养细胞进行的实验。这类体外研究无法提供关于体内实际发生情况的信息，因为所研究组织的解剖结构和生理功能已被破坏。因此，本研究的目的是探讨分离的大鼠肺模型在标准实验条件下用于表征大剂量注射后百草枯在该组织中的动力学行为的实用性，以及评估灌注培养基中用锂（Li+）等渗替代Na+的影响。所得结果表明，目前的分离大鼠肺模型可用于分析百草枯的毒代动力学，本文首次对此进行了报道。还观察到，灌注培养基中Na+的缺失导致分离的大鼠肺中百草枯的摄取减少，尽管似乎这种情况一旦除草剂到达组织的血管外结构后，对改善百草枯的清除并无帮助，因为在所检测的两种实验条件下，百草枯组织洗脱期相似。
