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从病理形态学角度测定猪体内顺二氯二氨铂化合物的毒性

[Determination of cis-diamminedichloroplatinum compound toxicity in pigs from the viewpoint of pathomorphology].

作者信息

Neuhybel P, Beránek L, Zert Z, Vorlícek J, Kleinwächter V, Kiss F

出版信息

Vet Med (Praha). 1982 May;27(5):275-82.

PMID:6808754
Abstract

The study is a part of the clinical testing of the cytostatic preparation PLATIDIAM --Lachema with cis-diammine-dichloroplatinum complex (cis/DDP) as an active ingredient. The organs and tissues of 18 test pigs weighing 31 to 55 kg were subjected to the patho-morphological examination. The animals had been given experimentally the test cytostatic preparation Platidiam at a rate of 2.5 and 4.0 mg cis-DDP per kg 1. w. with and without hydration of their organisms. Severe changes were recorded in the kidneys of the pigs given the toxic doses of cis-DDP (4 mg/kg l. w.). The most frequent finding was that of cylindrical protein blocks in renal tubules combined with hyalinization of tubule cells. Optical microscopy of marrow showed vacuolization of epithelium and peeling off of epithelium layers. In some cases the dystrophic changes in renal tubules even led to necrotization of epithelium. No such changes were observed in the remaining animals given the therapeutic doses (2.5 mg/kg l. w.) nor in the controls. The findings on other organs cannot be associated with the toxicity of cis/DDP.

摘要

该研究是细胞抑制制剂PLATIDIAM(拉赫马公司生产)——以顺二氨二氯铂络合物(顺铂/顺二氨二氯铂)作为活性成分的临床测试的一部分。对18头体重31至55千克的试验猪的器官和组织进行了病理形态学检查。这些动物通过实验给予了试验性细胞抑制制剂PLATIDIAM,剂量为每千克体重2.5毫克和顺铂/顺二氨二氯铂4.0毫克,且分别在机体有水合作用和无水合作用的情况下给药。在给予有毒剂量顺铂/顺二氨二氯铂(4毫克/千克体重)的猪的肾脏中记录到了严重变化。最常见的发现是肾小管中出现圆柱形蛋白质块,同时伴有肾小管细胞玻璃样变。骨髓的光学显微镜检查显示上皮细胞空泡化和上皮层脱落。在某些情况下,肾小管的营养不良性变化甚至导致上皮细胞坏死。在给予治疗剂量(2.5毫克/千克体重)的其余动物以及对照组中未观察到此类变化。在其他器官上的发现与顺铂/顺二氨二氯铂的毒性无关。

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