Distribution and speciation of arsenic after intravenous administration of monomethylmonothioarsonic acid in rats

Quite a few new thioarsenicals have recently been found in urine of arsenic-exposed humans and animals, and some of them have been shown to be highly toxic to cells. However, little is known about their toxic effects and metabolism in the body. In order to elucidate the toxic mechanism of thioarsenicals, we further focused on the distribution and metabolism of monomethylmonothioarsonic acid (MMMTAV) in rats. MMMTAV was synthesized chemically and injected intravenously into rats at the dose of 0.5 mg As/kg, followed by speciation analysis of selected organs and body fluids at 10 min and 12 h after the injection. MMMTAV was excreted into urine in its intact form, and approximately 35% of the dose was recovered in urine at 12 h after the injection, suggesting that MMMTAV was taken up more effectively by organs/tissues than non-thiolated, monomethylarsonous acid (MMAV) previously studied. On the other hand, the liver and kidneys contained arsenic that was in a protein-binding form with free forms of DMAV or DMDTAV at 10 min, and disappeared at 12 h after the injection. Moreover, these bound arsenic species in kidneys were converted back to MMAV after oxidation with H2O2, suggesting that the arsenic bound to proteins had been reduced within the body and was in a trivalent oxidation state. In red blood cells (RBCs), most of the arsenic was in the form of DMAIII bound to hemoglobin (Hb), and approximately 40% of the dose was recovered in RBCs at 12 h after injection. These results indicate that arsenic accumulated preferentially in RBCs after being transformed to DMAIII. In addition, we have also discussed the effect of MMMTAV on viability of human bladder cancer T24 cells in comparison with MMAV. Consequently, MMMTAV was assumed to be a more toxic arsenic metabolite than non-thiolated MMAV.