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Role of Glutathione Conjugation in 1-Bromobutane-induced Immunotoxicity in Mice

  • Received : 2010.05.18
  • Accepted : 2101.05.25
  • Published : 2010.06.01

Abstract

Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.

Keywords

References

  1. Anundi, I., Hogberg, J. and Stead, A.H. (1979). Glutathione depletion in isolated hepatocytes: its relation to lipid peroxidation and cell damage. Acta Pharmacol. Toxicol. (Copenh), 45, 45-51.
  2. B’Hymer, C. and Cheever, K.L. (2004). Development of a gas chromatographic test for the quantification of the biomarker 3-bromopropionic acid in human urine. J. Chromatogr. B, 802, 361-366. https://doi.org/10.1016/j.jchromb.2003.12.004
  3. Baillie, E.A. and Davis, M.R. (1993). Mass spectrometry in the analysis of glutathione conjugates. Biol. Mass. Spectrum., 22, 319-325. https://doi.org/10.1002/bms.1200220602
  4. Chasseaud, L.F. (1976). Conjugation with glutathione and mercapturic acid excretion in Glutathione Metabolism and Function (I.M. Arias and W.B. Jakoby, Eds.). Raven Press, New York, pp. 77-114.
  5. Droge, W., Schulze-Osthoff, K., Mihm, S., Galter, D., Schenk, H., Eck, H., Roth, S. and Gmunder, H. (1994). Functions of glutathione and glutathione disulfide in immunology and immunopathology. FASEB J., 8, 1131-1138.
  6. Elferink, J.G.R. and de Koster, B.M. (1991). Glutathione-induced enhancement of neutrophil locomotion. Immunobiol., 184, 25-36. https://doi.org/10.1016/S0171-2985(11)80569-3
  7. Ellman, G.L. (1959). Tissue sulfhydryl group. Arch. Biochem. Biophys., 82, 70-77.
  8. Gmunder, H., Roth, S., Eck, H.P., Gallas, H., Mihm, S. and Droge, W. (1990). Interleukin-2 mRNA expression, lymphokine production and DNA synthesis in glutathione-depleted T cells. Cell Immunol., 130, 520-528. https://doi.org/10.1016/0008-8749(90)90292-Y
  9. Han, E.H., Hwang, Y.P., Lee, K.J., Jeong, T.C. and Jeong, H.G. (2008). 1-Bromopropane induces macrophage activation via extracellular signal-regulated kinase 1/2 MAPK and $NF-{\kappa}B$ pathways. Cancer Lett., 262, 28-36. https://doi.org/10.1016/j.canlet.2007.11.024
  10. Haroldsen, P.E., Reilly, M.H., Hughes, H., Gaskell, S.J. and Porter, C.J. (1988). Characterization of glutathione conjugates by fast atom bombardment/tandem mass spectrometry. Biomed. Environ. Mass Spetrom., 15, 615-621. https://doi.org/10.1002/bms.1200151107
  11. James, S.P., Jeffery, D.A., Waring, R.H. and Wood, P.B. (1968). Some metabolites of 1-bromobutane in the rabbit and the rat. Biochem. J., 109, 727-736.
  12. Jeong, T.C., Cha, S.W., Park, J.I., Ha, C.S., Han, S.S. and Roh, J.K. (1995). Role of metabolism in ethyl carbamate-induced suppression of antibody response to sheep erythrocytes in female Balb/C mice. Int. J. Immunopharmac., 17, 1035-1044. https://doi.org/10.1016/0192-0561(95)00092-5
  13. Jones, A.R. and Walsh, D.A. (1979). The oxidative metabolism of 1-bromopropane in the rat. Xenobiotica, 9, 763-772. https://doi.org/10.3109/00498257909042344
  14. Khan, S. and O’Brien, P.J. (1991). 1-Bromoalkanes as new potent nontoxic glutathione depletors in isolated rat hepatocytes. Biochem. Biophys. Res. Commun., 179, 436-441. https://doi.org/10.1016/0006-291X(91)91389-T
  15. Lag, M., Søderlund, E.J., Omichinski, J.G., Brunborg, G., Holme, J.A., Dahl, J.E., Nelson, S.D. and Dybing, E. (1991). Effect of bromine and chlorine positioning in the induction of renal and testicular toxicity by halogenated propanes. Chem. Res. Toxicol., 4, 528-534. https://doi.org/10.1021/tx00023a007
  16. Lee, S.K., Lee, D.J., Jeong, H., Bista, S.R., Kang, M.J., Lee, E.S., Son, J.K., Nam, D.H., Chang, H.W., Lee, S.H., Jahng, Y. and Jeong, T.C. (2007a). Hepatotoxic and immunotoxic effects produced by 1,3-dibromopropane and its conjugation with glutathione in female BALB/c mice. J. Toxicol. Environ. Health A, 70, 1381-1390. https://doi.org/10.1080/15287390701434489
  17. Lee, S.K., Jeon, T.W., Kim, Y.B., Lee, E.S., Jeong, H.G. and Jeong, T.C. (2007b). Role of glutathione conjugation in the hepatotoxicity and immunotoxicity induced by 1-bromopropane in female BALB/c mice. J. Appl. Toxicol., 27, 358-367. https://doi.org/10.1002/jat.1214
  18. Lee, S.K., Jin, C.H., Hyun, S.H., Lee, D.W., Kim, G.H., Jeon, T.W., Lee, J., Kim, D.H., Jeong, H.G., Lee, E.S. and Jeong, T.C. (2005a). Identification of glutathione conjugates of 1,2-dibromopropane in female BALB/c mice by liquid chromatographyelectrospray ionization tandem mass spectrometry. Xenobiotica,35, 97-105. https://doi.org/10.1080/00498250400021937
  19. Lee, S.K., Jo, S.W., Jeon, T.W., Jun, I.H., Jin, C.H., Kim, G.H., Lee, D.J., Kim, T.O., Lee, E.S. and Jeong, T.C. (2005b). Hepatotoxic effect of 1-bromopropane and its conjugation with glutathione in male ICR mice. Arch. Pharm. Res., 28, 1177-1182. https://doi.org/10.1007/BF02972983
  20. Lee, S.K., Kang, M.J., Jeon, T.W., Ha, H.W., Yoo, J.W., Ko, G.S., Kang, W., Jeong, H.G., Lyoo, W.S. and Jeong, T.C. (2010). Role of metabolism in 1-bromopropane-induced hepatotoxicity in mice. J. Toxicol. Environ. Health A, in print.
  21. Lowry, O.H., Rosenbrough, N.J., Farr, A.L. and Randall, R.J. (1951). Protein measurement with the folin phenol reagent. J. Biol. Chem., 193, 265-275.
  22. Luster, M.I., Portier, C., Pait, D.G., White, K.L., Jr., Gennings, C., Munson, A.E. and Rosenthal, G.J. (1992). Risk assessment in immunotoxicology. I. Sensitivity and predictability of immune tests. Fund. Appl. Toxicol., 18, 200-210. https://doi.org/10.1016/0272-0590(92)90047-L
  23. Miccadel, S., Kyle, M., Gilfor, D. and Farber, J.L. (1988). Toxic consequence of the abrupt depletion of glutathione in cultured rat hepatocytes. Arch. Biochem. Biophys., 265, 311-320. https://doi.org/10.1016/0003-9861(88)90133-6
  24. Ozawa, N. and Guengerich, F.P. (1983). Evidence for formation of an S-[2-(N7-guanyl)ethyl]glutathione adduct in glutathionemediated binding of the carcinogen 1,2-dibromoethane to DNA. Proc. Natl. Acad. Sci., U.S.A., 80, 5266-5270. https://doi.org/10.1073/pnas.80.17.5266
  25. Pathak, N. and Khandelwal, S. (2006a). Influence of cadmium on murine thymocytes: potentiation of apoptosis and oxidative stress. Toxicol. Lett., 165, 121-132. https://doi.org/10.1016/j.toxlet.2006.02.004
  26. Pathak, N. and Khandelwal, S. (2006b). Oxidative stress and apoptotic changes in murine splenocytes exposed to cadmium. Toxicology, 220, 26-36. https://doi.org/10.1016/j.tox.2005.11.027
  27. Pathak, N. and Khandelwal, S. (2007). Role of oxidative stress and apoptosis in cadmium induced thymic atrophy and splenomegaly in mice. Toxicol. Lett., 169, 95-108. https://doi.org/10.1016/j.toxlet.2006.12.009
  28. Prohaska, J.R. (1980). The glutathione peroxidase activity of glutathione S-transferase. Biochim. Biophys. Acta, 611, 87-98. https://doi.org/10.1016/0005-2744(80)90045-5
  29. Roth, S. and Droge, W. (1991). Regulation of interleukin 2 production, interleukin 2 mRNA expression and intracellular glutathione levels in ex vivo derived T lymphocytes by lactate. Eur. J. Immunol., 21, 1933-1937. https://doi.org/10.1002/eji.1830210823
  30. Roth, S., Gmunder, H. and Droge, W. (1991). Regulation of intracellular glutathione levels and lymphocyte functions by lactate. Cell Immunol., 136, 94-104.
  31. Silva, J.M. and O’Brien, P.J. (1989). Allyl alcohol- and acroleininduced toxicity in isolated rat hepatocytes. Arch. Biochem. Biophys., 275, 551-558. https://doi.org/10.1016/0003-9861(89)90401-3
  32. Van Bladeren, P.J. (1983). Metabolic activation of xenobiotics: Ethylene dibromide and structural analogs. J. Am. Coll. Toxicol., 2, 73-83. https://doi.org/10.3109/10915818309140692
  33. Wu, D., Meydani, S.N. and Sastre, J. (1994). In vitro glutathione supplementation enhances interleukin-2 production and mitogenic response of peripheral blood mononuclear cells from young and old subjects. J. Nutr., 124, 655-663.
  34. Yamada, Y.K., Shimizu, F., Kawamura, R. and Kubota, K. (1981). Thymic atrophy in mice induced by cadmium administration. Toxicol. Lett., 8, 49-55. https://doi.org/10.1016/0378-4274(81)90137-5
  35. Younes, M. and Sieger, C.P. (1981). Mechanistic aspects of enhanced lipid peroxidation following glutathione depletion in vivo. Chem. -Biol. Interact., 34, 257-266. https://doi.org/10.1016/0009-2797(81)90098-3