Effects of endogenous hydrogen peroxide and glutathione on the stability of arsenic metabolites in rat bile
- Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan)
- Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan)
Trivalent arsenicals such as arsenite (iAs{sup III}), monomethylarsonous acid (MMA{sup III}) and dimethylarsinous acid (DMA{sup III}) are more toxic than analogous pentavalent compounds such as arsenate (iAs{sup V}), monomethylarsonic acid (MMA{sup V}) and dimethylarsinic acid (DMA{sup V}). It has been reported that arsenic-glutathione (As-GSH) complexes such as arsenic triglutathione (ATG) and methylarsenic diglutathione (MADG) are major metabolites in rat bile following intravenous administration of iAs{sup III}. Recently, we have shown that both ATG and MADG are unstable and easily hydrolyzed to iAs{sup III} and MMA{sup III}, respectively, and that MMA{sup III} is oxidized to MMA{sup V} in bile. In the present study we report the effects of H{sub 2}O{sub 2} and GSH on the stability of As-GSH complexes in rat bile. Male SD rats were injected intravenously with saline or iAs{sup III} at a dose of 0.2 or 2.0 mg As/kg body weight, and bile fluid was collected on ice for 30 min. To estimate the stability of As-GSH complexes in bile, ATG or MADG was added to untreated, heat-treated, catalase-treated, or dialyzed bile, and then incubated at 37 deg. C for 10 min. Concentrations of biliary H{sub 2}O{sub 2} and GSH in the higher dose group were 12.6- and 4.5-times higher than the control value, respectively. Exogenously added trivalent arsenicals were oxidized to pentavalent arsenicals in the bile depending on the biliary concentration of H{sub 2}O{sub 2}. Both catalase and dialysis prevented oxidation of trivalent arsenicals to the corresponding pentavalent compounds. Exogenously added GSH stabilized As-GSH complexes in bile. These results suggest that H{sub 2}O{sub 2} converts trivalent arsenicals to less toxic pentavalent arsenicals, whereas GSH prevents hydrolysis of As-GSH complexes and the generation of unconjugated toxic trivalent arsenicals.
- OSTI ID:
- 21144118
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 232, Issue 1; Other Information: DOI: 10.1016/j.taap.2008.06.003; PII: S0041-008X(08)00252-4; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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