Effect of selenite on the disposition of arsenate and arsenite in rats.
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.
Csanaky
Iván
I
Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, Szigeti út 12, H-7643, Pécs, Hungary.
Gregus
Zoltán
Z
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001149:Arsenates / Q000037:antagonists & inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D001152:Arsenicals / Q000097:blood / Q000652:urine; D018053:Arsenites / Q000037:antagonists & inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001711:Biotransformation; D002101:Cacodylic Acid / Q000097:blood / Q000652:urine; D004347:Drug Interactions; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018038:Sodium Selenite / Q000494:pharmacology*; D014018:Tissue Distribution
D001149:Arsenates; D001152:Arsenicals; D018053:Arsenites; C027579:periodate-oxidized adenosine; D002101:Cacodylic Acid; D018038:Sodium Selenite; C020300:monomethylarsonic acid; D000241:Adenosine