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大鼠气管内滴注氯化钇后的分布、定位及肺部效应

Distribution, localization, and pulmonary effects of yttrium chloride following intratracheal instillation into the rat.

作者信息

Hirano S, Kodama N, Shibata K, Suzuki K T

机构信息

National Institute for Environmental Studies, Ibaraki, Japan.

出版信息

Toxicol Appl Pharmacol. 1990 Jun 15;104(2):301-11. doi: 10.1016/0041-008x(90)90304-d.

Abstract

Metabolic behavior and pulmonary toxicity of yttrium chloride (YCl3) deposited in the lung was investigated. Yttrium chloride was instilled intratracheally into rats and the time-course and dose-related changes in distribution of Y between lung tissue and bronchoalveolar lavage fluid (BALF) and pulmonary inflammatory responses were investigated. Pulmonary clearance of Y was very slow and the half-life was estimated to be 168 days. Yttrium content in the supernatant of BALF did not exceed 5 micrograms Y/lung even when a dose of 200 micrograms Y/rat was administered, suggesting that the alveolar surface fluid could retain at most 5 micrograms Y. On the other hand, Y content in the pellet of BALF changed with the number of macrophages retrieved in BALF in both time-course and dose-response experiments. Transmission electron microscopy and X-ray microanalysis suggested that Y was localized in lysosomes of alveolar and interstitial macrophages, and basement membranes. These results clearly explain the long pulmonary half-life of Y. beta-Glucuronidase activity and calcium and phosphorous contents in the supernatant of BALF increased significantly even at the lowest dose (10 micrograms Y/rat). Comparative dose-effect profiles of lactate dehydrogenase activity in BALF supernatant revealed that 1 mol of YCl3 is equivalent to about one-third mole of cadmium compounds and about 3 mol of zinc oxide in the potency for acute pulmonary toxicity.

摘要

研究了沉积在肺中的氯化钇(YCl3)的代谢行为和肺毒性。将氯化钇经气管内注入大鼠体内,研究了肺组织与支气管肺泡灌洗液(BALF)中钇分布的时间进程和剂量相关变化以及肺部炎症反应。钇在肺部的清除非常缓慢,半衰期估计为168天。即使给予200微克钇/大鼠的剂量,BALF上清液中的钇含量也不超过5微克/肺,这表明肺泡表面液最多可保留5微克钇。另一方面,在时间进程和剂量反应实验中,BALF沉淀中的钇含量随BALF中回收的巨噬细胞数量而变化。透射电子显微镜和X射线微分析表明,钇定位于肺泡和间质巨噬细胞的溶酶体以及基底膜中。这些结果清楚地解释了钇在肺部的长半衰期。即使在最低剂量(10微克钇/大鼠)下,BALF上清液中的β-葡萄糖醛酸酶活性以及钙和磷含量也显著增加。BALF上清液中乳酸脱氢酶活性的比较剂量效应曲线显示,就急性肺毒性而言,1摩尔YCl3相当于约三分之一摩尔镉化合物和约3摩尔氧化锌。

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