Effect of selenite on the disposition of arsenate and arsenite in rats
Effect of selenite on the disposition of arsenate and arsenite in rats
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DOI：
10.1016/s0300-483x(02)00604-2
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发表时间：
2003-04-15
期刊：
影响因子：
4.5
通讯作者：
Gregus, Z
中科院分区：
文献类型：
--
作者：
Csanaky, I;Gregus, Z
亚硒酸盐（SeIV）和无机砷相互抵消毒性。SeIV抑制肝细胞中的砷甲基化，然而，尚不清楚它是否会减少高毒性单甲基larsonous酸（MMAsIII）的形成。因此，我们研究了与甲基化抑制剂高碘酸盐氧化腺苷（PAD）相比，SeIV （10 μ mol/kg，静脉注射）对大鼠血液、胆汁和尿液中砷代谢物的影响，以及静脉注射50 μ mol/kg亚砷酸盐（AsIII）或砷酸盐（AsV）时肝脏和肾脏中砷代谢物的分布。采用高效液相色谱-氢化物发生-原子荧光光谱法（HPLC-HG-AFS）分析砷代谢产物。在给予砷的大鼠中，PAD降低了甲基化砷代谢物（MMAsIII，单甲基拉森酸[MMAsV]和二甲基拉森酸[DMAsV]）的排泄和组织浓度，同时增加了AsV和AsIII的组织保留率。SeIV对砷处置的影响与PAD有显著差异。例如，在注射asii和asv的动物中，SeIV降低了MMAsIII和MMAsV的组织水平，但增加了DMAsV的水平。SeIV几乎消除了asv暴露大鼠的MMAsIII胆道排泄，但对asiii剂量大鼠几乎没有影响。sev诱导的。砷的处置在很大程度上可归因于含有三价砷和硒化物（Sell）的已知络合物的形成，这不仅取决于而且影响这些类金属物种在组织中的可用性和作用。通过这种络合作用，当三价砷的可用性有限时（例如在asv暴露的大鼠中），SeII损害砷的单甲基化，但当AsIII的存在是压倒性的（例如在AsIII剂量的大鼠中）时，它的影响较小。作为辅助发现，研究表明，未注射砷的大鼠的血液中也会出现DMAsV，并且可以通过测量血源性DMAsV的积累来跟踪大鼠的DMAsV形成。(C) 2002爱思唯尔科学爱尔兰有限公司版权所有。
Selenite (SeIV) and inorganic arsenicals counter the toxicity of each other. SeIV inhibits arsenic methylation in hepatocytes, however, it is unknown whether it decreases the formation of the highly toxic monomethylarsonous acid (MMAsIII). Therefore, we examined, in comparison with the methylation inhibitor periodate-oxidised adenosine (PAD), the effect of SeIV (10 mumol/kg, i.v.) on the appearance of arsenic metabolites in blood, bile and urine as well as the distribution of arsenic metabolites in the liver and kidneys in rats injected i.v. with 50 mumol/kg arsenite (AsIII) or arsenate (AsV). Arsenic metabolites were analysed by HPLC-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS). In rats given either arsenical, PAD decreased the excretion and tissue concentrations of methylated arsenic metabolites (MMAsIII, monomethylarsonic acid [MMAsV], and dimethylarsinic acid [DMAsV]), while increasing the tissue retention of AsV and AsIII. The effect of SeIV on arsenic disposition differed significantly from that of PAD. For example, both in ASIII- and AsV-injected animals, SeIV lowered the tissue levels of MMAsIII and MMAsV, but increased the levels of DMAsV. SeIV almost abolished the biliary excretion of MMAsIII in AsV-exposed rats, but barely influenced it in AsIII-dosed rats. The SeIV-induced changes in. arsenic disposition may largely be ascribable to formation of the known complex containing trivalent arsenic and selenide (Sell), which not only depends on but also influences the availability and effects of these metalloid species in tissues. By such complexation SeII compromises monomethylation of arsenic when trivalent arsenic availability is limited (e.g. in AsV-exposed rats), but affects it less when the presence of AsIII is overwhelming (e.g. in AsIII-dosed rats). As an auxiliary finding, it is shown that DMAsV occurs in the blood of rats not injected with arsenic and that DMAsV formation in rats can be followed by measuring the build-up of blood-borne DMAsV. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.