| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2571083 | Toxicology and Applied Pharmacology | 2008 | 8 Pages |
Thioarsenicals have been paid much attention due to the toxicity of arsenic, since some of them are highly toxic and commonly found in the urine of mammals. We previously reported that thioarsenicals might be produced in red blood cells (RBCs). Here, we further characterized the mechanism underlying the production and metabolism of thioarsenicals in RBCs using 34S-labeled dimethylmonothioarsinic acid (34S-DMMTAV) and purified rat hemoglobin (Hb) or a rat RBC lysate. 34S-DMMTAV did not bind to Hb on incubation with purified rat Hb, remaining in its original form. However, when 34S-DMMTAV was incubated with a rat RBC lysate, only arsenic, i.e., not sulfur (34S), was detected in a form bound to Hb (As-Hb). In addition, another arsenic product containing sulfur (34S) in the molar ratio of 34S/As = 2 was detected, which was assigned as dimethyldithioarsinic acid (DMDTAV), suggesting that arsenic does not bind to Hb in the form of 34S-DMMTAV but does so in the form of dimethylarsinous acid (DMAIII). Namely, DMMTAV appeared to be hydrolyzed into dimethylarsinic acid (DMAV) and H34S-, and the released H34S- reacted with DMMTAV to produce DMDTAV. Thus, DMMTAV was transformed into DMDTAV and DMAV (2DMMTAV - > DMDTAV + DMAV), the latter product being reduced to DMAIII in the presence of GSH and bound to Hb. In a separate experiment, 34S-DMMTAV was incubated with sulfide (Na2S) and GSH. Although DMMTAV was not transformed into DMDTAV in the presence of only Na2S or GSH, it was transformed into DMDTAV in the presence of both Na2S and GSH. Our results suggest that DMMTAV is hydrolyzed enzymatically into DMAV and sulfide, the former being reduced to DMAIII and bound to Hb, and the latter reacting with DMMTAV to yield DMDTAV. Thus, DMMTAV is transformed into DMDTAV and DMAV through a hydrolytic reaction in a manner similar to a disproportionation reaction, DMAV being reduced and bound to Hb (As-Hb), and DMDTAV being produced more in the presence of sulfides in the medium.
