Analysis of two new degradation products of arsenic triglutathione in aqueous solution

Abstract

Inorganic arsenicals, including arsenite (As^III) and arsenate (As^V), are well-known human carcinogens. Recently, studies have indicated that arsenic triglutathione (As(GS)₃) is unstable in an aqueous solution. The present study was designed to evaluate the degradation mechanism of As(GS)₃ in an aqueous solution using high-performance liquid chromatography-electrospray ionisation mass spectrometry (HPLC-ESI-MS). Based on the fragments obtained from MS² and MS³, we identified two new compounds: one was an isomer of glutathione (GSH), and the other was a product from the cleavage of the glutamyl of oxidised glutathione (GSSG). The isomerization of GSH resulted in the loss of its function such as detoxification of many reactive metabolites. The formation of the two new compounds affected the ratio of GSH/GSSG, and thus may affect the antioxidant and detoxification of GSH/GSSG in mammalian cells.

Keywords

arsenic triglutathione / glutathione / HPLC-ESI-MS

References

[1] Mandal B K, Suzuki K T. Arsenic round the world: a review. Talanta, 2002, 58(1): 201-235

[2] Bates M N, Smith A H, Hopenhayn-Rich C. Arsenic ingestion and internal cancers: a review. American Journal of Epidemiology, 1992, 135(5): 462-476

[3] Chen C J, Chen C W, Wu M M, Kuo T L. Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water. British Journal of Cancer, 1992, 66(5): 888-892

[4] Smith A H, Hopenhayn-Rich C, Bates M N, Goeden H M, Hertz-Picciotto I, Duggan H M, Wood R, Kosnett M J, Smith M T. Cancer risks from arsenic in drinking water. Environmental Health Perspectives, 1992, 97(6): 259-267

[5] Smith A H, Lingas E O, Rahman M. Contamination of drinking-water by arsenic in Bangladesh: a public health emergency. Bulletin of the World Health Organization, 2000, 78(9): 1093-1103

[6] Rahman M M, Chowdhury U K, Mukherjee S C, Mondal B K, Paul K, Lodh D, Biswas B K, Chanda C R, Basu G K, Saha K C, Roy S, Das R, Palit S K, Quamruzzaman Q, Chakraborti D. Chronic arsenic toxicity in Bangladesh and West Bengal, India—a review and commentary. Journal of Toxicology. Clinical Toxicology, 2001, 39(7): 683-700

[7] Petrick J S, Ayala-Fierro F, Cullen W R, Carter D E, Vasken Aposhian H. Monomethylarsonous acid (MMA(III)) is more toxic than arsenite in Chang human hepatocytes. Toxicology and Applied Pharmacology, 2000, 163(2): 203-207

[8] Styblo M, Del Razo L M, Vega L, Germolec D R, LeCluyse E L, Hamilton G A, Reed W, Wang C, Cullen W R, Thomas D J. Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells. Archives of Toxicology, 2000, 74(6): 289-299

[9] Thomas D J, Styblo M, Lin S. The cellular metabolism and systemic toxicity of arsenic. Toxicology and Applied Pharmacology, 2001, 176(2): 127-144

[10] Hirano S, Kobayashi Y, Cui X, Kanno S, Hayakawa T, Shraim A. The accumulation and toxicity of methylated arsenicals in endothelial cells: important roles of thiol compounds. Toxicology and Applied Pharmacology, 2004, 198(3): 458-467

[11] Jin Y, Sun G, Li X, Li G, Lu C, Qu L. Study on the toxic effects induced by different arsenicals in primary cultured rat astroglia. Toxicology and Applied Pharmacology, 2004, 196(3): 396-403

[12] Hayakawa T, Kobayashi Y, Cui X, Hirano S. A new metabolic pathway of arsenite: arsenic-glutathione complexes are substrates for human arsenic methyltransferase Cyt19. Archives of Toxicology, 2005, 79(4): 183-191

[13] Buchet J P, Lauwerys R. Role of thiols in the in-vitro methylation of inorganic arsenic by rat liver cytosol. Biochemical Pharmacology, 1988, 37(16): 3149-3153

[14] Anundi I, Högberg J, Vahter M. GSH release in bile as influenced by arsenite. FEBS Letters, 1982, 145(2): 285-288

[15] Ballatori N, Clarkson T W. Biliary secretion of glutathione and of glutathione-metal complexes. Fundamental and Applied Toxicology, 1985, 5(5): 816-831

[16] Kala S V, Neely M W, Kala G, Prater C I, Atwood D W, Rice J S, Lieberman M W. The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic. Journal of Biological Chemistry, 2000, 275(43): 33404-33408

[17] Raab A, Meharg A A, Jaspars M, Genney D R, Feldmann J. Arsenic-glutathione complexes-their stability in solution and during separation by different HPLC modes. Journal of Analytical Atomic Spectrometry, 2004, 19(1): 183-190

[18] Gailer J, Lindner W. On-column formation of arsenic-glutathione species detected by size-exclusion chromatography in conjunction with arsenic-specific detectors. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 1998, 716(1-2): 83-93

[19] Le X C, Lu X, Ma M, Cullen W R, Aposhian H V, Zheng B. Speciation of key arsenic metabolic intermediates in human urine. Analytical Chemistry, 2000, 72(21): 5172-5177

[20] Xie R, Johnson W, Spayd S, Hall G S, Buchley B. Arsenic speciation analysis of human urine using ion exchange chromatography coupled to ICP MS. Analytica Chimica Acta, 2006, 578(2): 186-194

[21] Raab A, Meharg A A, Jaspars M, Genney D R, Feldmann J J. Arsenic-glutathione complexes—their stability in solution during separation by different HPLC modes. Journal of Analytical Atomic Spectrometry, 2004, 19(1): 183-190

[22] Suzuki K T, Mandal B K, Ogra Y. Speciation of arsenic in body fluids. Talanta, 2002, 58(1): 111-119

[23] Scott N, Hatlelid K M, MacKenzie N E, Carter D E. Reactions of arsenic(III) and arsenic(V) species with glutathione. Chemical Research in Toxicology, 1993, 6(1): 102-106

[24] Delnomdedieu M, Basti M M, Otvos J D, Thomas D J. Reduction and binding of arsenate and dimethylarsinate by glutathione: a magnetic resonance study. Chemico-Biological Interactions, 1994, 90(2): 139-155

[25] Styblo M, Yamauchi H, Thomas D J. Comparative in vitro methylation of trivalent and pentavalent arsenicals. Toxicology and Applied Pharmacology, 1995, 135(2): 172-178

[26] Stýblo M, Thomas D J. In vitro inhibition of glutathione reductase by arsenotriglutathione. Biochemical Pharmacology, 1995, 49(7): 971-977

[27] Kanaki K, Pergantis S. Development of mass spectrometric methods for detecting arsenic-glutathione complexes. Journal of the American Society for Mass Spectrometry, 2008, 19(10): 1559-1567

[28] Akerboom T P, Bilzer M, Sies H J. The relationship of biliary glutathione disulfide efflux and intracellular glutathione disulfide content in perfused rat liver. Biological Chemistry, 1982, 257(8): 4248-4252

[29] Fahey R C. Biologically important thiol-disulfide reactions and the role of cyst(e)ine in proteins: an evolutionary perspective. Advances in Experimental Medicine and Biology, 1977, 86(A): 1-30

[30] Armstrong R N. Structure, catalytic mechanism, and evolution of the glutathione transferases. Chemical Research in Toxicology, 1997, 10(1): 2-18

[31] Eaton D L, Bammler T K. Concise review of the glutathione S-transferases and their significance to toxicology. Toxicological Sciences, 1999, 49(2): 156-164

[32] Hayes J D, Flanagan J U, Jowsey I R. Glutathione transferases. Annual Review of Pharmacology and Toxicology, 2005, 45(1): 51-88

[33] Nobili V, Pastore A, Gaeta L M, Tozzi G, Comparcola D, Sartorelli M R, Marcellini M, Bertini E, Piemonte F. Glutathione metabolism and antioxidant enzymes in patients affected by nonalcoholic steatohepatitis. Clinica Chimica Acta, 2005, 355(1-2): 105-111

Acknowledgments

This work was supported by a grant from the National High Technology Research and Development Program of China (863 Program) (No. 2012AA063504), and Project of Ocean with Scientific Technology in Tianjin (KJXH2011-10).

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg