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通过给小鼠施用砷对肝锌硫蛋白进行化学形态依赖性诱导以及联合施用硒的影响

Chemical form-dependent induction of hepatic zinc-thionein by arsenic administration and effect of co-administered selenium in mice.

作者信息

Maitani T, Saito N, Abe M, Uchiyama S, Saito Y

机构信息

National Institute of Hygienic Sciences, Tokyo, Japan.

出版信息

Toxicol Lett. 1987 Nov;39(1):63-70. doi: 10.1016/0378-4274(87)90257-8.

DOI:10.1016/0378-4274(87)90257-8
PMID:3672556
Abstract

Four arsenic compounds (m-arsenite, arsenate, methylarsonate (MMA), and dimethylarsinate (DMA) were administered to mice, either orally or by intraperitoneal injection, and the amounts of induced hepatic zinc-thionein (Zn-Th) were determined to investigate the chemical form dependency in metallothionein induction by arsenic. Several mice died within 24 h following intraperitoneal injection. The toxicity estimated from the lethality was in the order of m-arsenite greater than arsenate much greater than DMA approximately equal to MMA. Although all 4 arsenic compounds more or less induced Zn-Th following intraperitoneal injection, the dose of inorganic arsenic compounds observed to cause induction was one order lower than that of organic arsenic compounds. The induction of hepatic Zn-Th was also observed following oral administration, and inorganic arsenic compounds were again found to be more effective inducers via this route. To study the interactions of m-arsenite and selenite with regard to the amounts of Zn-Th induced, the two compounds were co-administered intraperitoneally. The amount of hepatic Zn-Th induced by the co-administration was one-fifth of that observed after selenite administration, and was almost the same as that after m-arsenite injection. Namely, when co-administered m-arsenite had the effect of lowering the level of Zn-Th induced following selenite administration, but the converse phenomenon was not observed.

摘要

将四种砷化合物(间亚砷酸盐、砷酸盐、甲基胂酸(MMA)和二甲基胂酸(DMA))通过口服或腹腔注射给予小鼠,并测定诱导产生的肝锌硫蛋白(Zn-Th)的量,以研究砷诱导金属硫蛋白过程中对化学形态的依赖性。腹腔注射后24小时内有几只小鼠死亡。根据致死率估算的毒性顺序为:间亚砷酸盐>砷酸盐>>DMA≈MMA。尽管腹腔注射后所有4种砷化合物或多或少都能诱导产生Zn-Th,但观察到能引起诱导的无机砷化合物的剂量比有机砷化合物低一个数量级。口服给药后也观察到肝Zn-Th的诱导情况,并且再次发现无机砷化合物通过这种途径是更有效的诱导剂。为了研究间亚砷酸盐和亚硒酸盐在诱导Zn-Th量方面的相互作用,将这两种化合物腹腔联合给药。联合给药诱导产生的肝Zn-Th量是亚硒酸盐给药后观察到的量的五分之一,并且与间亚砷酸盐注射后的量几乎相同。也就是说,联合给药时,间亚砷酸盐具有降低亚硒酸盐给药后诱导产生的Zn-Th水平的作用,但未观察到相反的现象。

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