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인간 간세포주 에서 포름알데히드에 의한 세포 사멸 효과

Apoptotic effect of formaldehyde in cultured human hepatocyte cell lines

  • 박수현 (전남대학교 수의과대학 바이오치료 산업인력 양성팀, 동물의학 연구소)
  • Park, Soo-Hyun (Bio-therapy Human Resources Center, Animal Medical Center, Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University)
  • 발행 : 2009.12.30

초록

Exposure of formaldehyde (FA), one of the major compounds in pesticides and in the onset of sick house syndrome, has been implicated in the development of diverse diseases. Liver is a very important organ to body metabolism and drug detoxification. Apotosis of hepatocytes is associated with the onset of liver diseases such as hepatitis. However, the apoptotic effect of FA in hepatocytes is not clear. Therefore, this study was conducted to investigate the effect of FA on the apoptosis in HepG2 cells, a human hepatocyte cell line. As a result, FA (> $500\;{\mu}M$) decreased cell viability and increased lactate dehydrogenase activity in HepG2 cells, which was blocked by the treatment of vitamin E and N-acetylcysteine (NAC). In addition, FA decreased glutathione (GSH) contents and Bcl-2 levels, while increasing lipid peroxide formation and Bax levels. It also cleaved caspase-3 form, which was blocked by the treatment of vitamin E and NAC. It is insisted that FA induced apoptosis via oxidative stress in human hepatocytes.

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참고문헌

  1. Bagchi, D., Bagchi, M., Hassoun, E.A. and Stohs, S. J. (1993) Detection of paraquat-induced in vivo lipid peroxidation by gas chromatography/mass spectrometry and high-pressure liquid chromatography. J. Anal. Toxicol. 17, 411-414 https://doi.org/10.1093/jat/17.7.411
  2. Kita, T., Fujimura, M., Myou, S., Ishiura, Y., Abo, M., Katayama, N., Nishitsuji, M., Yoshimi, Y., Nomura, S., Oribe, Y. and Nakao, S. (2003) Potentiation of allergic bronchoconstriction by repeated exposure to formaldehyde in guinea-pigs in vivo. Clin Exp Allergy 33, 1747-1753 https://doi.org/10.1111/j.1365-2222.2003.01826.x
  3. Nakazawa, H., Ikeda, H., Yamashita, T., Hara, I., Kumai, Y., Endo, G. and Endo, Y. (2005) A case of sick building syndrome in a Japanese office worker. Ind Health. 43, 341-345 https://doi.org/10.2486/indhealth.43.341
  4. Callas, P.W., Pastides, H., and Hosmer, D. W. Jr. (1996) Lung cancer mortality among workers in formaldehyde industries. J Occup Environ Med. 38: 747-748 https://doi.org/10.1097/00043764-199608000-00006
  5. Collins, J.J., Acquavella, J.F. and Esmen, N.A. (1997) An updated meta-analysis of formaldehyde exposure and upper respiratory tract cancers. J Occup Environ Med. 39, 639-651 https://doi.org/10.1097/00043764-199707000-00009
  6. Kaplowitz, N. (2002) Biochemical and cellular mechanisms of toxic liver injury. Semin Liver Dis. 22, 137-144 https://doi.org/10.1055/s-2002-30100
  7. Webb, C. and Twedt, D. (2008) Oxidative stress and liver disease. Vet Clin North Am Small Anim Pract. 38, 125-135 https://doi.org/10.1016/j.cvsm.2007.10.001
  8. Ghavami, S., Hashemi, M., Kadkhoda, K., Alavian, S. M., Bay, G. H. and Los, M. (2005) Apoptosis in liver diseases-detection and therapeutic applications. Med Sci Monit. 11(11), RA337-RA345
  9. Faubel, S. and Edelstein, C. L. (2005) Caspases as drug targets in ischemic organ injury. Curr Drug Targets Immune Endocr Metabol Disord. 5(3), 269-287 https://doi.org/10.2174/1568008054863754
  10. Albano, E., Rundgren, M., Harvison, P.J.. Nelson, S.D. and Moldeus, P. (1985) Mechanisms of N-acetylp- benzoquinone imine cytotoxicity. Mol. Pharmacol. 28, 306-311
  11. Fujimaki, H., Kurokawa, Y., Kunugita, N., Kikuchi, M., Sato, F. and Arashidani, K. (2004) Differential immunogenic and neurogenic inflammatory responses in an allergic mouse model exposed to low levels of formaldehyde. Toxicology. 197, 1-13 https://doi.org/10.1016/j.tox.2003.11.015
  12. Park, S. H. (2009) Involvement of oxidative stress in formaldehyde-induced apoptosis in cultured lung macrophage cells. Kor. J. of Environ. Agri. 28, 295-300 https://doi.org/10.5338/KJEA.2009.28.3.295
  13. Meister, A. (1991) Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy. Pharmacol Ther. 51, 155-194 https://doi.org/10.1016/0163-7258(91)90076-X
  14. Teng, S., Beard, K., Pourahmad, J., Moridani, M., Easson, E., Poon, R. and O'Brien, P. J. (2001) The formaldehyde metabolic detoxification enzyme systems and molecular cytotoxic mechanism in isolated rat hepatocytes. Chem Biol Interact. 130-132: 285-296 https://doi.org/10.1016/S0009-2797(00)00272-6
  15. Koivusalo, M. and Uotila, L. (1993) Glutathionedependent formaldehyde dehydrogenase/class III alcohol dehydrogenase: further characterization of the rat liver enzyme. Adv Exp Med Biol. 328, 465-474 https://doi.org/10.1007/978-1-4615-2904-0_49
  16. Skrzydlewska, E. and Farbiszewski, R. (1999) Protective effect of N-acetylcysteine on reduced glutathione, reduced glutathione-related enzymes and lipid peroxidation in methanol intoxication. Drug Alcohol Depend. 57, 61-67 https://doi.org/10.1016/S0376-8716(99)00040-X
  17. Gulec, M., Gurel, A. and Armutcu, F. (2006) Vitamin E protects against oxidative damage caused by formaldehyde in the liver and plasma of rats. Mol Cell Biochem. 290, 61-67 https://doi.org/10.1007/s11010-006-9165-z
  18. Guha, M., Kumar, S., Choubey, V., Maity, P. and Bandyopadhyay, U. (2006) Apoptosis in liver during malaria: role of oxidative stress and implication of mitochondrial pathway. FASEB J. 20, 1224-1226 https://doi.org/10.1096/fj.05-5338fje
  19. Tong, Q. S., Zheng, L. D., Tang, S. T., Jiang, G. S., Ruan, Q. L., Zeng, F. Q. and Dong, J. H. (2007) Nitrofen suppresses cell proliferation and promotes mitochondria-mediated apoptosis in type II pneumocytes. Acta Pharmacol Sin. 28, 672-684 https://doi.org/10.1111/j.1745-7254.2007.00552.x
  20. Sul, D., Kim, H., Oh, E., Phark, S., Cho, E., Choi, S., Kang, H. S., Kim, E. M., Hwang, K. W. and Jung, W. W. (2007) Gene expression profiling in lung tissues from rats exposed to formaldehyde. Arch Toxicol. 81, 589-597 https://doi.org/10.1007/s00204-007-0182-9
  21. San-Miguel, B,, Alvarez, M., Culebras, J.M,, Gonzalez- Gallego, J. and Tunon, M. J. (2006) N-acetyl-cysteine protects liver from apoptotic death in an animal model of fulminant hepatic failure. Apoptosis. 11, 1945-1957 https://doi.org/10.1007/s10495-006-0090-0