Arsenic metabolism and thioarsenicals in hamsters and rats.
The tissue distribution and chemical forms of arsenic were compared in two animal species with different metabolic capacity and toxicity to arsenic. Hamsters and rats were given a single oral dose of arsenite (iAsIII) at 5.0 mg As/kg body weight, and then the concentrations of arsenic were determined; more than 75% of the dose accumulated in rat red blood cells (RBCs) in the form of dimethylarsinous acid (DMAIII), whereas less than 0.8% of the dose accumulated in hamster RBCs, mostly in the form of monomethylarsonous acid (MMAIII). Reflecting the low accumulation in RBCs, more than 63% of the dose was recovered in hamster urine within one week (7.8-fold higher than that in rat urine). The quantity of arsenic distributed in the liver and kidneys was significantly higher in hamsters than in rats, and arsenic in livers stayed much longer in hamsters than in rats. Arsenic accumulated more and was retained longer in the kidneys than in the livers in both animals, and in hamster kidneys, it accumulated at levels higher than those in rat kidneys in the form of MMAIII bound to proteins. In the first 24 h urine, dimethylmonothioarsinic (DMMTAV) and dimethyldithioarsinic (DMDTAV) acids were detected in hamsters, but only DMMTAV was found in rats, together with an unknown arsenic metabolite in both animals. The unknown urinary arsenic metabolite was identified as monomethylmonothioarsonic acid (MMMTAV; CH3As(=S)(OH)2). The present results indicate that in hamsters, arsenic does not accumulate in RBCs, and therefore, hamsters exhibit a more uniform tissue distribution and faster urinary excretion of arsenic than rats. In addition, arsenic was thiolated more in hamsters than in rats excreting mono and dimethylated thioarsenicals in urine.
Naranmandura
Hua
H
Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Suzuki
Noriyuki
N
Iwata
Katsuya
K
Hirano
Seishiro
S
Suzuki
Kazuo T
KT
D000284:Administration, Oral; D000818:Animals; D001151:Arsenic / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D006224:Cricetinae; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008745:Methylation; D009928:Organ Specificity / Q000187:drug effects; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013885:Thiosulfates / Q000494:pharmacology; D013997:Time Factors; D014556:Urine
D013438:Sulfhydryl Compounds; D013885:Thiosulfates; D001151:Arsenic