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大鼠静脉注射氯化钇的代谢与毒性

Metabolism and toxicity of intravenously injected yttrium chloride in rats.

作者信息

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

机构信息

Environmental Health Sciences Division, National Institute for Environmental Studies, Ibaraki, Japan.

出版信息

Toxicol Appl Pharmacol. 1993 Aug;121(2):224-32. doi: 10.1006/taap.1993.1149.

Abstract

Although radioactive yttrium (Y) has been used for medical treatment, little attention has been directed toward the toxicity of Y. We report time-course and dose-related changes in tissue distribution, subcellular localization, clearance, and acute toxicity of iv-injected yttrium chloride (YCl3) in rats. Intravenously injected Y was predominantly distributed to plasma in the blood. At doses more than 0.2 mg Y/rat, most plasma Y appears to be in colloidal material which was composed of proteins and some minerals. Electron microscopic analyses revealed that the colloidal material was taken up by phagocytic cells in the liver and spleen. The liver Y was slowly cleared with a half-time of 144 days at a dose of 1 mg Y/rat. Glutamic-oxaloacetic and glutamic-pyruvate transaminase activities in blood plasma were increased with a peak at 20 hr postinjection at a dose of 1 mg Y/rat and returned to their control values at 170 hr postinjection, indicating that iv-injected YCl3 caused acute hepatic injury. Some of the plasma Ca was translocated to the colloidal material and plasma Ca concentration was increased transiently following injection of YCl3, probably because of resorption of bone. At a dose of 1 mg Y/rat, a significant and tremendous amount of Ca was deposited in the liver (over 10-fold) and spleen (over 100-fold), while Ca concentration was only slightly increased in the lung and kidney (less than 1.5-fold). These results indicate that the liver and spleen are primary target organs of iv-injected YCl3.

摘要

尽管放射性钇(Y)已被用于医学治疗,但人们对钇的毒性关注甚少。我们报告了静脉注射氯化钇(YCl3)在大鼠体内的组织分布、亚细胞定位、清除情况及急性毒性的时间进程和剂量相关变化。静脉注射的钇主要分布于血液中的血浆。在剂量超过0.2 mg Y/大鼠时,大部分血浆钇似乎存在于由蛋白质和一些矿物质组成的胶体物质中。电子显微镜分析显示,这种胶体物质被肝脏和脾脏中的吞噬细胞摄取。以1 mg Y/大鼠的剂量,肝脏中的钇清除缓慢,半衰期为144天。在1 mg Y/大鼠的剂量下,注射后20小时血浆中谷氨酸草酰乙酸转氨酶和谷氨酸丙酮酸转氨酶活性升高并达到峰值,在注射后170小时恢复到对照值,表明静脉注射YCl3引起急性肝损伤。部分血浆钙转移至胶体物质中,注射YCl3后血浆钙浓度短暂升高,这可能是由于骨吸收所致。在1 mg Y/大鼠的剂量下,大量的钙显著沉积在肝脏(超过10倍)和脾脏(超过100倍)中,而肺和肾脏中的钙浓度仅略有升高(小于1.5倍)。这些结果表明,肝脏和脾脏是静脉注射YCl3的主要靶器官。

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