Csanaky Iván, Gregus Zoltán
Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, Szigeti út 12, H-7643, Pécs, Hungary.
Toxicology. 2003 Apr 15;186(1-2):33-50. doi: 10.1016/s0300-483x(02)00604-2.
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 micromol/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 micromol/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 (SeII), 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.
亚硒酸盐（SeIV）与无机砷化物可相互拮抗毒性。SeIV可抑制肝细胞中的砷甲基化，然而，其是否会减少剧毒的一甲基亚砷酸（MMAsIII）的形成尚不清楚。因此，我们将SeIV（10微摩尔/千克，静脉注射）与甲基化抑制剂高碘酸盐氧化腺苷（PAD）进行比较，研究其对静脉注射50微摩尔/千克亚砷酸盐（AsIII）或砷酸盐（AsV）的大鼠血液、胆汁和尿液中砷代谢产物的出现情况以及肝脏和肾脏中砷代谢产物分布的影响。通过高效液相色谱-氢化物发生-原子荧光光谱法（HPLC-HG-AFS）分析砷代谢产物。在给予任一砷化物的大鼠中，PAD降低了甲基化砷代谢产物（MMAsIII、一甲基砷酸[MMAsV]和二甲基砷酸[DMAsV]）的排泄和组织浓度，同时增加了AsV和AsIII在组织中的潴留。SeIV对砷代谢的影响与PAD显著不同。例如，在注射AsIII和AsV的动物中，SeIV均降低了MMAsIII和MMAsV的组织水平，但增加了DMAsV的水平。SeIV几乎消除了AsV暴露大鼠中MMAsIII的胆汁排泄，但对AsIII给药大鼠的影响微乎其微。SeIV引起的砷代谢变化可能主要归因于已知的含三价砷和硒化物（SeII）复合物的形成，这不仅取决于这些类金属物质在组织中的可用性和作用，还会对其产生影响。通过这种络合作用，当三价砷的可用性有限时（如在AsV暴露的大鼠中），SeII会损害砷的一甲基化，但当AsIII大量存在时（如在AsIII给药的大鼠中），其影响较小。作为一项辅助发现，研究表明未注射砷的大鼠血液中存在DMAsV，并且通过测量血液中DMAsV的积累可以追踪大鼠体内DMAsV的形成。
