Cadmium-induced apoptosis in the urogenital organs of the male rat and its suppression by chelation.
Cadmium-induced apoptosis in the urogenital organs of the male rat and its suppression by chelation.
复制标题
DOI：
10.1080/00984109708984058
复制
发表时间：
1997-10
期刊：
影响因子：
--
通讯作者：
Heping Yan;C. Carter;Cunyong Xu;Pramod K. Singh;Mark M. Jones;Joyce E. Johnson;Mary S. Dietrich
中科院分区：
文献类型：
--
作者：
Heping Yan;C. Carter;Cunyong Xu;Pramod K. Singh;Mark M. Jones;Joyce E. Johnson;Mary S. Dietrich
在体内，0.03 mmol/kg镉剂量给药48小时后，雄性Wistar大鼠泌尿生殖系统的多个器官出现了镉诱导的细胞凋亡。在肾脏、前列腺、精囊、睾丸和附睾中发现了特征性的DNA断裂（通过酶联免疫吸附试验测定）和组织病理学观察到的细胞凋亡特征变化。TUNEL实验也显示细胞凋亡。膀胱和输精管组织没有这种变化。及时给予能够到达细胞内镉结合位点的适当螯合剂可以抑制导致细胞凋亡的过程。ELISA结果显示，镉处理大鼠1小时后给予单异酰基介索-2,3-二巯基琥珀酸（Mi-ADMS, 0.5 mmol/kg i.p）拮抗剂，可有效减少细胞凋亡的典型组织病理学迹象和相关的染色质DNA断裂。在正常时间使用螯合剂会导致DNA更大程度地降解为寡核苷酸，并在大鼠泌尿生殖系统的受影响器官中出现更明显的细胞凋亡变化的组织病理学证据。TUNEL试验也表明，随着拮抗剂在镉后使用的时间间隔逐渐增加，凋亡变化也逐渐增加。
Cadmium-induced apoptosis is shown to occur, in vivo, in several organs of the male Wistar rat urogenital system, 48 h after cadmium administration i.p. at a dose of 0.03 mmol/kg. Characteristic DNA fragmentation (as measured by an enzyme-linked immunosorbent-assay, ELISA) and histopathologically observed changes characteristic of apoptosis are found in the kidney, prostate, seminal vesicles, testes, and epididymis. TUNEL assay also demonstrates the apoptosis. Such changes are absent from bladder and vas deferens tissue. Timely administration of an appropriate chelating agent capable of reaching intracellular cadmium binding sites can suppress the processes leading to apoptosis. Administration of monoisomyl meso-2,3-dimercaptosuccinate (Mi-ADMS, 0.5 mmol/kg i.p.) to cadmium-treated rats is effective in greatly reducing typical histopathologic signs of apoptosis and the associated chromatin DNA fragmentation as revealed by ELISA when the antagonist is administered 1 h after cadmium. Administration of the chelating agent at law times results in greater degradation of DNA into oligonucleotides and more prominent histopathological evidence of apoptotic changes in the affected organs of the rat urogenital system. There is also a progressive increase in apoptotic changes indicated by TUNEL assay, as the antagonist is administered at progressively greater intervals after cadmium.