55094-22-9Relevant articles and documents
Animal species difference in the uptake of dimethylarsinous acid (DMAIII) by red blood cells
Shiobara,Ogra,Suzuki
, p. 1446 - 1452 (2001)
The animal species difference in the metabolism of arsenic was studied from the viewpoint of the mechanism underlying its distribution in the form of dimethylated arsenic in red blood cells (RBCs). Dimethylarsinic (DMAV) and dimethylarsinous (DMAIII) acids were incubated with rat, hamster, mouse, and human RBCs, and the uptake rates and chemical forms of arsenic were determined. Although DMAV was practically not or taken up slowly by RBCs of all the present animal species, DMAIII was taken efficiently in the order of rat > hamster > human, RBCs of mice taking it up less efficiently and with a different pattern from the former three animals. Further, although DMAIII taken up by rat RBCs was retained, that by hamster ones was effluxed in the form of DMAV. The uptake of DMAIII and efflux of DMAV took place much more slowly in human RBCs than rat and hamster ones. The uptake of DMAIII by RBCs was inhibited on the oxidation of glutathione with diamide. Incubation of DMAIII, but not of DMAV, with a hemolysate produced a high molecular weight complex, which increases in the presence of glutathione, suggesting that DMAIII taken up by RBCs is retained through the formation of a complex with protein(s) specific to animal species, and effluxed from RBCs after being oxidized to DMAV. These results indicate that DMA is taken up by RBCs in the form of DMAIII, and that the uptake and efflux rates are dependent on the animal species, the effluxed arsenic being DMAV. The present results suggest that the uptake of DMA by RBCs is an additional contributing factor to the animal species difference in the metabolism of arsenic in addition to the reduction and methylation capacity in the liver.
Theoretical calculations and reaction analysis on the interaction of pentavalent thioarsenicals with biorelevant thiol compounds
Suzuki, Noriyuki,Naranmandura, Hua,Hirano, Seishiro,Suzuki, Kazuo T.
, p. 550 - 553 (2008/12/22)
To obtain a rational understanding of the extraordinary interaction of pentavalent thioarsenicals with biorelevant thiol compounds, we carried out ab initio calculations on related arsenic compounds and discussed the correlation between the distribution of observed arsenic species in actual reaction systems and the corresponding calculated reaction enthalpies. Previously, it was considered that pentavalent arsenicals do not form thiol conjugates. However, the dimethylmonothioarsinic acid-glutathione conjugate (DMMTAV-GSH) was recently reported as the first stable conjugate of a pentavalent arsenical with a thiol compound. We carried out detailed analysis of the DMMTA V-GSH formation reaction and demonstrated that this conjugate could be formed nonenzymatically under weakly acidic conditions. On the basis of the ab initio calculations, this conjugation was an exothermic reaction (ΔH = -4.85 kcal/mol) and gave the minimum energy point during the reaction sequence of DMMTAV with a thiol compound. However, in the case of dimethylarsinic acid (DMAV), a corresponding oxo acid to DMMTA V, conjugation with a thiol compound is an endothermic reaction (ΔH = +0.06 kcal/mol). The minimum energy point of the reaction sequence of DMAV with a thiol compound was the formation of a trivalent dimethylarsinous acid (DMAIII)-GSH conjugate. Because the formation of arsenic-sulfur bonds is one of the major mechanisms for arsenic toxicity, these energetic results could account for the extraordinary behaviors and toxicities of thioarsenicals in vivo and in vitro in comparison with those of the corresponding oxo acids.
Glutathione-conjugated arsenics in the potential hepato-enteric circulation in rats
Suzuki,Tomita,Ogra,Ohmichi
, p. 1604 - 1611 (2007/10/03)
The metabolic pathways for arsenic were precisely studied by determining the metabolic balance and chemical species of arsenic to gain an insight into the mechanisms underlying the animal species difference in the metabolism and preferential accumulation of arsenic in red blood cells (RBCs) in rats. Male Wistar rats were injected intravenously with a single dose of arsenite (iAsIII) at 2.0 mg of As/kg of body weight, and then the time-dependent changes in the concentrations of arsenic in organs and body fluids were determined. Furthermore, arsenic in the bile was analyzed on anion and cation exchange columns by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). The metabolic balance and speciation studies revealed that arsenic is potentially transferred to the hepato-enteric circulation through excretion from the liver in a form conjugated with glutathione (GSH). iAsIII is methylated to mono (MMA)- and dimethylated (DMA) arsenics in the liver during circulation in the conjugated form [iAsIII(GS)3], and a part of MMA is excreted into the bile in the forms of MMAIII and MMAv, the former being mostly in the conjugated form [CH3AsIII(GS)2], and the latter being in the nonconjugated free form. DMAIII and DMAv were not detected in the bile. In the urine, arsenic was detected in the forms of iAsIII, arsenate, MMAv, and DMAv, iAsIII being the major arsenic in the first 6-h-urine, and DMAv being increased in the second 6-h-urine. The present metabolic balance and speciation study suggests that iAsIII is methylated in the liver during its hepato-enteric circulation through the formation of the GSH-cojugated form [iAsIII(GS)3], and MMAIII and MMAv are partly excreted into the bile, the former being in the conjugated form [CH3AsIII(GS)2]. DMA is not excreted into the bile but into the bloodstream, accumulating in RBCs, and then excreted into the urine mostly in the form of DMAv in rats.
