Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Hepatotoxic Effect of 1-Bromopropane and Its Conjugation with Glutathione in Male ICR Mice

  • Lee Sang Kyu (College of Pharmacy, Yeungnam University) ;
  • Jo Sang Wook (College of Pharmacy, Yeungnam University) ;
  • Jeon Tae Won (College of Pharmacy, Yeungnam University) ;
  • Jun In Hye (College of Pharmacy, Yeungnam University) ;
  • Jin Chun Hua (College of Pharmacy, Yeungnam University) ;
  • Kim Ghee Hwan (College of Pharmacy, Yeungnam University) ;
  • Lee Dong Ju (College of Pharmacy, Yeungnam University) ;
  • Kim Tae-Oh (School of Civil and Environmental Engineering, Kumoh National Institute of Technology) ;
  • Lee Eung-Seok (College of Pharmacy, Yeungnam University) ;
  • Jeong Tae Cheon (College of Pharmacy, Yeungnam University)
  • Published : 2005.10.01
Download PDF
⟨ Previous Next ⟩

Abstract

The hepatotoxic effects of 1-bromopropane (1-BP) and its conjugation with glutathione were investigated in male ICR mice. A single dose (1000 mg/kg, po) of 1-BP in corn oil to mice significantly increased serum activities of alanine aminotransferase and aspartate aminotransferase. Glutathione (GSH) content was dose-dependently reduced in liver homogenates 12 h after 1-BP treatment. In addition, 1-BP treatment dose-dependently increased levels of S-pro-pyl GSH conjugate at 12 h after treatment, as measured by liquid chromatography-electro-spray ionization tandem mass spectrometry. The GSH conjugate was maximally increased in liver at 6 h after 1-BP treatment (1000 mg/kg), with a parallel depletion of hepatic GSH content. Finally, 1-BP induced the production of malondialdehyde in liver. The present results suggest that 1-BP might cause hepatotoxicity, including lipid peroxidation via the depletion of GSH, due to the formation of GSH conjugates in male ICR mice.

Keywords

References

  1. B'Hymer, C. and Cheever, K. L., Development of a gas chromatographic test for the quantification of the biomarker 3-bromopropionic acid in human urine. J. Chromatogr., B, 802, 361-366 (2004) https://doi.org/10.1016/j.jchromb.2003.12.004
  2. Dalton, T. P., Chen, Y., Schneider, S. N., Nebert, D. W., and Shertzer, H. G., Genetically altered mice to evaluate glutathione homeostasis in health and disease. Free Radic. Biol. Med., 37, 1511-1526 (2004) https://doi.org/10.1016/j.freeradbiomed.2004.06.040
  3. Ellman, G. L., Tissue sulfhydryl group. Arch. Biochem. Biophys., 82, 70-77 (1959) https://doi.org/10.1016/0003-9861(59)90090-6
  4. Humphreys, W. G., Kim, D. H., and Guengerich, F. P., Isolation and characterization of $N^7$-guanyl adducts derived from 1,2-dibromo-3-chloropropane. Chem. Res. Toxicol., 4, 445-453 (1991) https://doi.org/10.1021/tx00022a008
  5. Ichihara, G., Kitoh, J., Yu, X., Asaeda, N., Iwai, H., and Kumazawa, T., 1-Bromopropane, an alternative to ozone layer-depleting solvents, is dose-dependently neurotoxic to rats in long-term inhalation exposure. Toxicol. Sci., 55, 116-123 (2000) https://doi.org/10.1093/toxsci/55.1.116
  6. Ishidao, T., Kunugita, N., Fueta, Y., Arashidani, K., and Hori, H., Effects of inhaled 1-bramopropane vapor on rat metabolism. Toxicol. Lett., 134, 237-243 (2002) https://doi.org/10.1016/S0378-4274(02)00171-6
  7. Jones, A. R. and Walsh, D. A., The oxidative metabolism of 1-bromopropane in the rat. Xenobiotica, 9, 763-772 (1979) https://doi.org/10.3109/00498257909042344
  8. Kim, D. H. and Guengerich, F. P., Formation of the DNA adduct S-2-($N^7$-guanyl)ethyl glutathione from ethylene dibromide: effects of modulation of glutathione and glutathione Stransferase levels and lack of a role for sulfation. Carcinogenesis, 11, 419-424 (1990) https://doi.org/10.1093/carcin/11.3.419
  9. Kim, D. H., Humphreys, W. G., and Guengerich, F. P., Characterization of S-2-(M-adenyl)ethyl glutathione as an adduct formed in RNA and DNA from 1,2-dibromoethane. Chem. Res. Toxicol., 3, 587-594 (1990) https://doi.org/10.1021/tx00018a015
  10. Kim, N. H., Hyun, S. H., Jin, C. H., Lee, S. K., Lee, D. W., Jeon, T. W., Choi, C. B., Lee, E. S., Chae, W., and Jeong, T. C., Acute effects of 2-bromopropane and 1,2-dibromopropane on hepatotoxic and immunotoxic parameters in female BALB/c mice. Arch. Pharm. Res., 26, 943-950 (2003) https://doi.org/10.1007/BF02980204
  11. Kim, K. W., Kim, H. Y., Park, S. S., Jeong, H. S., Park, S. H., Lee, J. Y., Jeong, J. H., and Moon, Y. H., Gender differences in activity and induction of hepatic microsomal cytochrome P450 by 1-bromopropane in Sprague-Dawley rats. J. Biochem. Mol. Biol., 32, 232-238 (1999)
  12. Kosower, N. S. and Kosower, E. M., The glutathione status of cells. Int. Rev. Cytol. 54, 109-160 (1978) https://doi.org/10.1016/S0074-7696(08)60166-7
  13. Kyle, M. E., Sakaida, I., Serroni, A., and Farber, J. L., Metabolism of acetaminophen by cultured rat hapatocytes. Biochem. Pharmacol., 40, 1211-1218 (1990) https://doi.org/10.1016/0006-2952(90)90385-X
  14. Lee, E. S., Moon, Y. S., Zhao, L. X., Kim, E, Lim, H. T., Basnet, A., Jeong, T. C., and Chae, W., Synthesis, characterization, in vitro and calf thymus DNA identification of $N^7$-guanine adducts of 1- and 2-bromopropane. Toxicol, Sci., 72(S-1), 996 (2003)
  15. 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., Identification of glutathione conjugates of 1,2-dibromopropane in female BALB/c mice by liquid chromatography-electrospray ionization tandem mass spectrometry. Xenobiotica, 35, 97-105 (2005) https://doi.org/10.1080/00498250400021937
  16. Loughlin, A. F., Skiles, G. L., Alberts, D. W., and Schaefer, W. H., An ion exchange liquid chromatography/mass spectrometry method for the determination of reduced and oxidized glutathione and glutathione conjugates in hepatocytes. J. Pharmaceut. Biomed., 26, 131-142 (2001) https://doi.org/10.1016/S0731-7085(01)00402-2
  17. Lowry, O. H., Rosenbrough, N. J., Farr, A. L., and Randall, R. J., Protein measurement with the folin phenol reagent. J. Biol. Chem., 193, 265-275 (1951)
  18. Moldeus, P., Paracetamol metabolism and toxicity in isolated hepatocytes from rat and mouse. Biochem. Pharmacol., 27, 2859-2863 (1978) https://doi.org/10.1016/0006-2952(78)90201-0
  19. Ohkawa, H., Ohishi, N., and Yagi, K., Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 95, 351-358 (1979) https://doi.org/10.1016/0003-2697(79)90738-3
  20. Prabhu, S., Fackett, A., Lloyd, S. McClellan, H. A., Terrell, C. M., Silber, P. M., and Li, A. P., Identification of glutathione conjugates of troglitazone in human hepatocytes. Chem. Res. Toxicol., 142, 83-97 (2002)
  21. Tornero-Velez, R., Ross, M. K., Granville, C., Laskey, J., Jones, J. P., DeMarini, D. M., and Evans, M. V., Metabolism and mutagenicity of source water contaminants 1,3-dichloropropane and 2,2-dichloropropane. Drug Metab. Dispos., 32, 123-131 (2004) https://doi.org/10.1124/dmd.32.1.123
  22. Wang, H., Ichihara, G., Ito, H., Kato, K., Kitoh, J., Yamada, T., Yu, X., Tsuboi, S., Moriyama, Y., Sakatani, R., Shibata, E., Kamijima, M., Itohara, S., and Takeuchi, Y., Biochemical changes in the central nervous system of rats exposed to 1-bromopropane for seven days. Toxicol. Sci., 67, 114-120 (2002) https://doi.org/10.1093/toxsci/67.1.114
  23. Wang, H., Ichihara, G., Ito, H., Kato, K., Kitoh, J., Yamada, T., Yu, X., Tsuboi, S., Moriyama, Y., and Takeuchi, Y., Dosedependent biochemical changes in rat central nervous system after 12-week exposure to 1-bromopropane. Neurotoxicology, 24, 199-206 (2003) https://doi.org/10.1016/S0161-813X(02)00195-X
  24. Yu, X., Ichihara, G., Kitoh, J., Xie, Z., Shibata, E., and Kamijima, M., Preliminary report on the neurotoxicity of 1-bromopropane, an alternative solvent for chlorofluorocarbons. J. Occup. Health, 40, 234-235 (1998) https://doi.org/10.1539/joh.40.234
  25. Zhao, L. X., Kim, E., Lim, H. T., Moon, Y. S., Kim, N. H., Kim, T. H., Choi, H. S., Chae, W., Jeong, T. C., and Lee, E. S., Synthesis, characterization and in vitro identification of $N^7$-guanine adduct of 2-bromopropane. Arch. Pharm. Res., 25, 39-44 (2002) https://doi.org/10.1007/BF02975258