알코올 투여 방법이 흰쥐의 간과 뇌에서 산화적 스트레스유발에 미치는 영향

Effect of Different Ethanol Treatments on the Oxidative Stress in Liver and Brain of SD Rats

  • 박민경 (청운대학교 식품영양학과) ;
  • 이영재 (제주대학교 수의학과)
  • 발행 : 2002.09.01

초록

본 연구에서는 알코올 섭취 방법이 간과 뇌에서 산화적 스트레스 유발 정도에 미치는 영향을 알아보고자 횐쥐에 5%의 에탄올이 함유된 물을 1개월간 자유로이 섭취하게 하는 방법 또는 2.5g/kg의 에탄올을 1일 1회 1개월간 경구 투여하는 방법 등 알코올 투여 방법을 달리하고 간, 대뇌 및 소뇌에서 지질과산화 반응과 비타민 E의 함량 변화를 비교하였다. 5%-EtOH군의 간조직에서는 비타민 E의 함량이 증가하고 지질과산화물은 변화가 없었으며, 2.5g-EtOH군의 간조직에서는 비타민 E의 함량은 변화가 없으나 지질과산화물은 유의적으로 증가하였다. 뇌 조직에서는, 5%-EtOH군의 대뇌와 소뇌 모두에서 지질과산화물이 증가하고 비타민 E의 함량이 감소하였다. 또한, 2.5g-EtOH군의 대뇌와 소뇌에서도 지질과산화물이 증가하고 비타민 E의 함량이 감소하였으며 그 정도는, 5%-EtOH군에서 보다 큰 경향을 보였다. 결론적으로, 간에서의 지질과산화 반응 및 비타민 E의 함량은 알코올 투여 방법에 따라 다양하게 나타났으나 대뇌와 소뇌에서는 본 연구에서 실시한 투여 방법 모두에 의해 산화적 스트레스가 유발되었다.

The effect of different ethanol feeding protocols on the oxidative stress in liver and blain of rats was studied. The rats were fed 5%-ethanol solution in drinking water (5%-EtOH group) or 2.5g ethanol/kg body wt. once daily intragastrically (2.5g-EtOH group). The levels of thiobarbituric acid reactive substances (TRARS) and vitamin EI in the liver, cerebrum and cerebellum were measured. In the liver of 5%-EtOH group, the level of TBARS was not changed, whereas vitamin I was significantly increased compared to control group. In the liver of 2.5g-EtOH group, the level of TBARS was significantly increased compared to control group and the vitamin E concentration was not affected. The levels of TBARS were increased and the vitamin E concentrations were decreased significantly both in the cerebrum and cerebellum in 5%-EtOH group as well as in 2.5g-EtOH group. These results show that lipid peroxidation and vitamin E concentration in liver were varied according to the conditions of ethanol treatment, however, the vitamin E contents in cerebrum and cerebellum were affected by both ethanol intoxications used in this study.

키워드

참고문헌

  1. Nordmann, R., Ribiere, C. and Rouach, H: Implication of free radical mechanisms in ethanol-induced cellular injury. Free Radic. Biol. Med., 12, 219-240(1992) https://doi.org/10.1016/0891-5849(92)90030-K
  2. Bohr, V, Anson, R.M., Mazur, S. and Dianov, G: Oxidative DNA damage processing and changes with aging. Toxicol. Lett., 102, 47-52(1998) https://doi.org/10.1016/S0378-4274(98)00280-X
  3. Diluzio, N.R. and Hartman, A.D: Role of lipid peroxidation in the pathogenesis of ethanol-induced fatty liver. Fed. Proc., 26, 1436-1442(1967)
  4. Niki, E., Saito, T., Kawakami, A. and Kamiya, A: Inhibition of oxidation of methyllinolate in solution by vitamin E and vitamin C. J. Biol. Chem., 259, 4177-4182(1984)
  5. Sadrzadeh, S.M., Nanji, A.A. and Meydani, M: Effect of chronic ethanol feeding on plasma and liver alpha- and gamma-tocopherol levels in normal and vitamin E-deficient rats. Relationship to lipid peroxidation. Biochem. Pharmacol., 47, 2005-2010(1994) https://doi.org/10.1016/0006-2952(94)90075-2
  6. Vatassery, G.T: Vitamin E and other endogenous antioxidants in the central nervous system. Geriatrics, 53, S25-S27(1998)
  7. Cardozo-Pelaez, F., Brooks, P.J., Stedeford, T., Song, S. and Sanchez-Ramos, J: DNA damage, repair, and antioxidant systems in brain regions: a correlative study. Free Radic. Biol. Med., 28, 779-785(2000) https://doi.org/10.1016/S0891-5849(00)00172-6
  8. Mihara, M., Uchiyama, M. and Fukuzawa, K: Thiobarbituric acid value on fresh homogenate of rat as a parameter of lipid peroxidation in aging, CCl_4 intoxication and vitamin E deficiency. Biochem. Med., 23, 302-311(1980) https://doi.org/10.1016/0006-2944(80)90040-X
  9. Vatassery, G.T. and Hagen D.F: A liquid chromatographic method for quantitative determination of $\alpha$-tocopherol in rat brain. Anal. Biochem., 79, 129-134(1997) https://doi.org/10.1016/S0300-9084(97)81504-0
  10. Westerberg, E., Friberg, M. and Akesson, B: Assay of brain tocopherols using high performance liquid chromatography. J. Liquid Chromatography, 4, 109-121(1981) https://doi.org/10.1080/01483918108064801
  11. Ingelman-Sundberg, M., Ronis, M.J., Lindros, K.O, Eliasson, E. and Zhukov, A: Ethanol-inducible cytochrome P4502E1 :regulation, enzymology and molecular biology. Alcohol Alcohol Suppl., 2, 131-139(1994)
  12. Moore, D.R., Reinke, L.A. and McCay, P.B: Metabolism of ethanol to 1-hydroxyethyl radicals in vivo :detection with intravenous administration of alpha-(4-pyridyl-1- oxide)-N-t-butylnitrone. Mol. Pharmacol., 47, 1224-1230(1995)
  13. Cunnmgham, C.C. and Bailey, S,M: Ethanol consumption and liver mitochondria function. Biol. Signals Recept., 10, 271-282(2001) https://doi.org/10.1159/000046892
  14. Shaw, S. and Jayatilleke, E: The role of cellular oxidases and catalytic iron in the pathogenesis of ethanol-induced liver injuiy. Life Sci., 50, 2045-2052(1992) https://doi.org/10.1016/0024-3205(92)90570-F
  15. Whitfield, J.B., Zhu, H., Heath, A.C., Powell, L.W. and Martin, N.G: Effects of alcohol consumption on indices of iron stores and of iron stores on alcohol intake makers. Alcohol Clin. Exp. Res., 25, 1037-1045(2001) https://doi.org/10.1111/j.1530-0277.2001.tb02314.x
  16. Meydani, M., Seitz, H.K., Blumberg, J.B. and Russell, R.M: Effect of chronic ethanol feeding on hepatic and extrahepatic distribution of vitamin E in rats. Alcohol Clin. Exp. Res., 15, 771-774(1991) https://doi.org/10.1111/j.1530-0277.1991.tb00598.x
  17. Wisniewska-Knypl, J.M. and Wronska-Nofer, T: Biological markers of oxidative stress induced by ethanol and iron overload in rat. Int. J. Occup. Med. Environ. Health., 7, 355-363(1994)
  18. Coudray, C., Richard, M.J., Faure, H. and Favier, A: Blood and liver lipid peroxide status after chronic ethanol administration in rats. Clin. Chim. Acta., 129, 35-45(1993)
  19. Rouach, H., Fataccioli, V., Gentil, M., French, S.W, Morimoto, M. and Nordmann, R: Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology. Hepatology, 25, 351-355(1997) https://doi.org/10.1002/hep.510250216
  20. Eaton, S., Record, C.O. and Bartlett, K: Multiple biochemical effects in the pathogenesis of alcoholic fatty liver. Eur. J. Clin. Invest., 27, 719-722(1997) https://doi.org/10.1046/j.1365-2362.1997.1780727.x
  21. Bjorneboe, A., Bjomeboe, G.E., Hagen, B.F. and Drevon, C.A: Acute and chronic effects of ethanol on secretion of alpha-tocopherol from primary cultures of rat hepatocytes. Biochim. Biophys. Acta, 922, 357-363(1987) https://doi.org/10.1016/0005-2760(87)90059-2
  22. Anandatheerthavarada, H.K., Shankar, S.K., Bhamre, S., Boyd, M.R., Song, B.J. and Ravindraath, V: Induction of brain cytochrome P-450IIE1 by chronic ethanol treatment. Brain Res., 601, 279-285(1993) https://doi.org/10.1016/0006-8993(93)91721-4
  23. Sohda, T., Shimizu, M., K.amimura, S. and Okumura, M: Immunohistochemical demonstration of ethanol-inducible P450 2E1 in rat brain. Alcohol Alcohol Suppl., 1B, 69-75(1993)
  24. Rouach, H., Houze, P., Gentil. M., Orfanelli, M.T. and Nordmann, R: Changes in some pro-and antioxidants in rat cerebellum after chronic alcohol intake. Biochem. Pharmacol., 53, 539-545(1997) https://doi.org/10.1016/S0006-2952(96)00770-8
  25. Renis, M., Calabrese, V., Russo, A., Calderone, A., Barcellona, M.L. and Rizza V. Nuclear DNA strand breaks during ethanol-induced oxidative stress in rat brain. FEBS Lett., 390, 153-156(1996) https://doi.org/10.1016/0014-5793(96)00647-3
  26. Agar, E., Bosnak, M., Amanvermez, R., Demir, S., Ayyildiz, M. and Celik, C: The effect of ethanol on lipid peroxidation and glutathione level in the brain stem of rat. Neuroreport, 10, 1799-1801(1999) https://doi.org/10.1097/00001756-199906030-00032
  27. Martin, A., Prior, R., Shukitt-Hale, B., Cao, G. and Joseph, J.A: Effect of fruits, vegetables, or vitamin E-rich diet on vitamins E and C distribution in peripheral and brain tissues. J. Gerontol., 55, B144-6151(2001)