You are here:
Preabsorptive Metabolism of Sodium Arsenate by Anaerobic Microbiota of Mouse Cecum Forms a Variety of Methylated and Thiolated Arsenicals
Citation:
PINYAYEV, T., M. J. KOHAN, K. HERBIN-DAVIS, JOHN T. CREED, AND D. J. THOMAS. Preabsorptive Metabolism of Sodium Arsenate by Anaerobic Microbiota of Mouse Cecum Forms a Variety of Methylated and Thiolated Arsenicals. CHEMICAL RESEARCH IN TOXICOLOGY. American Chemical Society, Washington, DC, 24(4):475-477, (2011).
Impact/Purpose:
Develop analytical approaches to quantify reactive intermediates within the metabolic pathway of arsenic to enhance the mode of action / metabolism research (within NHEERL) and to develop the bioavailability / bioaccessibility research (within NERL). By developing species specific bioaccessibility estimates of inorganic arsenic in demographically harvested target foods it becomes possible to estimate population based exposures using probabilistic models like SHEDS.
Description:
The conventional scheme for arsenic methylation accounts for methylated oxyarsenical production but not for thioarsenical formation. Here, we report that in vitro anaerobic microbiota of mouse cecum converts arsenate into oxy- and thio- arsenicals. Besides methylarsonic acid (MMAV), arsenate was transformed into six unique metabolites: mono-, di-, and trithio-arsenic acid, monomethyldithio- and monomethyltrithio-arsonic acid, and dimethyldithioarsonic acid. Thioarsenicals were found in soluble and particulate fractions of reaction mixtures, suggesting interactions with anaerobic microbiota. Metabolism of ingested arsenate to oxy- and thio-arsenicals before absorption across the gastrointestinal barrier could affect bioavailability, systemic distribution, and resulting toxicity.