Dimercaptan metal-binding agents influence the biotransformation of arsenite in the rabbit.
Dimercaptan metal-binding agents influence the biotransformation of arsenite in the rabbit.
复制标题
二硫醇金属结合剂影响兔子体内亚砷酸盐的生物转化。
DOI：
10.1016/0041-008x(85)90323-0
复制
发表时间：
1985
影响因子：
3.8
通讯作者：
Aposhian,HV
中科院分区：
文献类型：
--
作者：
Maiorino,RM;Aposhian,HV
在给予亚砷酸钠和水溶性二硫醇的兔子中研究了亚砷酸钠的尿液代谢物。 1小时后，给兔子皮下注射NaAsO2(1mg As/kg)，给予0.2mmol/kg的盐水、2,3-二巯基-1-丙磺酸(DMPS)、内消旋二巯基琥珀酸(DMSA)或N-(2,3-二巯基丙基)邻苯二甲酰胺(DMPA)。通过组合阴离子-阳离子交换色谱法分离从治疗的兔子收集的尿液中的砷代谢物。对柱级分进行酸消解，并通过直接氢化物火焰原子吸收分光光度法分析砷。仅服用亚砷酸钠的兔子 0 至 24 小时尿液中发现的无机砷、胂酸甲酯和胂酸二甲酯的相对含量与口服亚砷酸钠的人类受试者的报告结果非常一致。这一发现表明兔子生物转化亚砷酸盐的方式与人类非常相似。施用二硫醇后，0至24小时内总砷的尿排泄量升高，但0至48小时内总砷的尿排泄量不受影响。该结果表明这些二硫醇的作用发生在治疗后早期。此外，二硫醇对0至24小时期间尿液中砷代谢物的排泄量有不同的影响。 DMPS、DMSA 或 DMPA 增加亚砷酸盐的排泄，但减少二甲基胂酸盐的排泄。 DMPS 或 DMPA 处理增加了甲基胂酸盐的排泄，但 DMSA 则没有。 DMPS 或 DMSA 处理后砷酸盐排泄增加，但不受 DMPA 处理影响。这些结果表明，二硫醇除了增加砷的排泄之外，还影响亚砷酸盐向毒性较小的物质的生物转化。对砷代谢物尿排泄的不同影响表明，这些二硫醇金属结合剂除了无机砷的简单螯合外还具有作用机制。
The urinary metabolites of sodium arsenite have been investigated in rabbits given sodium arsenite and water-soluble dimercaptans. Rabbits injected sc with NaAsO2(1 mg As/kg) were given, im 1 hr later, either saline, 2,3-dimercapto-1-propanesulfonic acid (DMPS), meso-dimercaptosuccinic acid (DMSA), or N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA) at 0.2 mmol/kg. Arsenic metabolites in urine collected from treated rabbits were isolated by combined anion-cation-exchange chromatography. Column fractions were acid-digested and analyzed for arsenic by direct hydride-flame atomic absorption spectrophotometry. The relative amounts of inorganic arsenic, methylarsonate, and dimethylarsinate found in 0 to 24 hr urine of rabbits given only sodium arsenite agreed closely with those reported for human subjects given arsenite po. This finding suggests that the rabbit biotransforms arsenite in a manner very similar to that of man. The urinary excretion of total arsenic between 0 and 24 hr was elevated after dimercaptan administration, but urinary excretion of total arsenic between 0 and 48 hr was unaffected. This result indicates that the action of these dimercaptans occurs early after treatment. In addition, the dimercaptans influenced differently the amounts of the arsenic metabolites excreted in the urine between 0 and 24 hr. DMPS, DMSA, or DMPA increased arsenite excretion but decreased dimethylarsinate excretion. DMPS or DMPA treatment increased methylarsonate excretion but DMSA did not. Arsenate excretion increased after DMPS or DMSA treatment but was not affected by DMPA treatment. These results suggest that the dimercaptans, in addition to increasing arsenic excretion, also influence the biotransformation of arsenite to less toxic species. The different effects on the urinary excretion of arsenic metabolites suggest that these dimercaptan metal binding agents have mechanisms of action in addition to simple chelation of inorganic arsenic.