Distributions and chemical forms of arsenic after intravenous administration of dimethylarsinic and monomethylarsonic acids to rats.
The observed toxicity of arsenic is highly dependent on animal species and differences in metabolism. Rats are one of the most tolerant species, and the metabolic pathway is quite different in some aspects from those of other mammals. The distinct metabolic pathway including the preferential accumulation in red blood cells (RBCs) has been explained, whereby allowing an effective use of rats as an animal model for the arsenic metabolism. In the present study, distributions of arsenic among organs/tissues/body fluids and their chemical forms were studied after intravenous injection of arsenic in the forms of dimethylarsinic (DMA(V)) and monomethylarsonic acids (MMA(V)) to rats. DMA(V) and MMA(V) were mostly excreted into urine immediately after the injection as the intact forms, and both forms were taken up less effectively by organs/tissues than arsenite. The methylated arsenics distributed in organs/tissues were excreted directly into urine and excreted before being redistributed in RBCs. DMA(V) and MMA(V) taken up by the liver were transformed to metabolites not yet identified, accumulated transiently in the liver, and then they disappeared from the liver. The unidentified metabolites were assumed to be transformed from dimethylarsinic acid (DMA(III)) following the consecutive metabolic reactions [MMA(V) --> monomethylarsonous acid (MMA(III)) --> DMA(V) --> DMA(III)]. The unidentified metabolites were excreted not into the bile but into the bloodstream. Injections of DMA(V) and MMA(V) induced a biliary excretion of arsenic but only at 0.2-0.3% of the dose, the arsenic in the bile being their intact free forms.
Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan. ktsuzuki@p.chiba-u.ac.jp
Kazuo T
KT
Suzuki
Akio
A
Katagiri
Yoko
Y
Sakuma
Yasumitsu
Y
Ogra
Masayoshi
M
Ohmichi
D000818:Animals; D001152:Arsenicals / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D002101:Cacodylic Acid / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D006540:Herbicides / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D001152:Arsenicals; D006540:Herbicides; D002101:Cacodylic Acid; C020300:monomethylarsonic acid