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研究生:湯勝輝
研究生(外文):Sheng-Hui Tang
論文名稱:酒精對酒癮患者毒性機轉的探討
論文名稱(外文):The Mechanisms of Ethanol Toxicity in Alcohol Dependence
指導教授:彭福佐
指導教授(外文):Fu-Chuo Peng
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:毒理學研究所
學門:醫藥衛生學門
學類:其他醫藥衛生學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:71
中文關鍵詞:氧化壓力酒精依賴超氧化陰離子MDA抗氧化狀態
外文關鍵詞:alcohol dependenceoxidative stressantioxidants statusMDAantioxidants statu
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本篇目的主要探討酒精依賴患者酒精依賴與其體內氧化壓力的相關性。我們分析76位酒精依賴患者的臨床生化指標及其體內的抗氧化狀態,以無飲酒相關問題的19位健康成人為對照族群。在酒精依賴患者臨床生化指標上,AST、ALT、γ-GT、T-Bilirubin、ALP、Cholesterol及Uric Acid等項目在酒精依賴患者的血液,對於對照無飲酒族群的血液皆有有意義之增加(p < 0.05),T-Protein則為有意義減少(p < 0.05)。在血清MDA濃度方面,相較於對照族群,酒精依賴患者血清MDA濃度也有明顯較高的現象(p < 0.05),而且經過戒斷治療後,血清MDA濃度有顯著的降低。在抗氧化防禦系統方面,血清中SOD、GSH及GPx的活性比對照族群降低了84%、15%及44%(p < 0.05),而GR輕微減少,CAT活性則有輕微的增加,但無統計意義。
酒癮族群經過14天戒斷治療後,血清中SOD、CAT及GPx活性比對照族群降低了81%、43%及52%(p < 0.05)。GSH及GR則是輕微絳低或沒有變化,不過並無統計意義。酒癮患者產生酒精依賴期間,時間長短和血清中MDA濃度是有相關性的(r = 0.538;p <0.001),也就是飲酒量的多寡和血清中MDA濃度的高低有關。此外,血清中CAT及GSH活性,對於血清中MDA濃度也是有相關性的(r = 0.701, 0.706;p <0.001)。以週邊血液做In vitro的實驗中,單ㄧ劑量給予乙醇或乙醛處理,將導致嗜中性白血球產生超氧化陰離子。根據實驗結果我們認為,產生酒癮期間將導致氧化壓力的增加,促進體內抗氧化物質耗竭,降低抗氧化系統防禦能力。

The aim of this study is to examine the relationship between alcohol dependence and oxidative stress. The biochemical parameters and antioxidants status are measured among 76 patients with alcohol dependence. Nineteen healthy persons without drinking problem are recruited as the control subjects. The AST, ALT, γ-GT, T-Bilirubin, ALP, Cholesterol and uric acid showed significant increasing in the blood specimen of patients as compared with those of the control subjects (p < 0.05). The serum T-Protein showed significant decreasing in the specimen of patients as compared with those of the control subjects (p < 0.05). Serum MDA of the patients was found to be significantly (p < 0.05) increased compared with those of the control subjects and decreased after abstinence. SOD, GSH and GPx activities in which were, respectively, 84%, 15%and 44% lower in alcoholic patients than in the control subjects (p < 0.05, respectively), whereas the change of GR and CAT activity were not statistically significant. After 14 days’ abstinence, SOD activity was reduced by 81% (p < 0.05), CAT by 43% (p < 0.05) and GPX by 52% (p < 0.05) in the patients, whereas the change of GSH and GR was not significant. The levels of MDA was significantly correlated with the duration of alcohol dependence (r = 0.538; p <0.001). In addition, the activities of CAT and GSH were significantly correlated with MDA levels (r = 0.701, 0.706 respectively; p < 0.001). In the vitro experiment of the treatment of peripheral blood with ethanol or acetaldehyde, superoxide anion was detected by flowcytometry. The results of present study suggest that oxidative stress occurred and caused subsequently exhaustion of the antioxidants during alcohol dependence.

表目錄…………………………………………………………………Ⅱ
圖目錄…………………………………………………………………Ⅲ
中文摘要………………………………………………………………Ⅵ
英文摘要………………………………………………………………Ⅷ
縮寫表…………………………………………………………………Ⅹ


第一章 緒 言……………………………………………………………1
第二章 實驗材料與方法 ………………………………………………9
第三章 實驗結果………………………………………………………24
第四章 討 論…………………………………………………….……29
第五章 參考文獻………………………………………………………35
附表 ……………………………………………………………………45
附圖 ……………………………………………………………………48


Albert, Y. S., Magnus, I. S., Etienne, N., Matsumoto, H., Nishitani, Y., Minowa, Y., Fukui, Y., Bailey, S. M., Patel, V. B., Carol C. C., Tomas Z., Lenka F., Ludmila M., Ptr P., Ivan M., Marta J., Karel N., and Grace Y. S. 2001. Ethanol and oxidative stress. Alcoholism: Clin. Expe. Res. 25 (5): 237S-243S.
Aoshima, T., Umetsu, K., Yuasa, I., Watanabe, G., Suzuki, T. 1998. Simultaneous genotyping of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) loci by amplified product length polymorphism (APLP) analysis. Electrophoresis 19: 659-660.
Barber, A. A., Bernheim, F. 1967. Lipid peroxidation: its measurement, occurrence, and significance in animal tissues. Adv. Gerontol. Res. 2: 355-403.
Bautista, A. P., Spitzer, J. J. 1992. Acute ethanol intoxication stimulates superoxide anion production by in situ perfused rat liver. Hepatology 15: 892-898.
Carlberg, I., and Mannervik, B. 1985. Glutathione reductase. Methods Enzymol. 113:484-499.
Carten, WO., and Robinson, J. P. 1994. Intracellular hydrogen peroxide and superoxide anion detection in endothelial cells. J. Leukocyte Biol. 55:253-258.
Chen, C. C., Kuo, C. J., Tsai, S. Y., and Yin, S. J. 2004. Relation of genotypes of alcohol metabolizing enzymes and mortality of liver diseases in patients with alcohol dependence. Addiction Biology (in press).
Chen, C. C., Kuo, C. J., and Tasi, S. Y. 2001. Cause of death of the patients with substance dependence: a record-linkage study in a psychiatric hospital in Taiwan. Addiction 96:729-736.
Chen, C. C., Lu, R. B., Chen, Y. C., Wang, M. F., Chang, Y. C., Li, T. K., Yin, S. J. 1999. Interaction between the functional polymorphisms of the alcohol-metabolizing genes in protection against alcoholism. Am. J. Hum. Genet. 65: 795-807.
Chen, C. J., Liang, K. Y., Chang, A. S., Chang, Y. C., Lu, C. N., Liaw, Y. F., Chang, W. Y., Sheen, M. C., and Lin, T. M. 1991. Effects of hepatitis B virus, alcohol drinking, cigarette smoking and familial tendency on hepatocellular carcinoma. Hepatology 13:398-406.
Cheng, ATA., Chen, W. J. 1995. Alcoholism among four aboriginal groups in Taiwan: high prevalences and their implications. Alcoholism: Clin. Exp. Res. 19: 81-91.
Clot, P., Tabone, M., Arico, S., and Albano, E. 1994. Mornitoring oxidative damage in patients with liver cirrhosis and different daily alcohol intake. Gut. 35:1637-1643.
Comporti, M. 1985. Lipid peroxidation and cellular damage in toxic liver injury. Lab. Invest. 53: 599-623.
Conigrave, K. M., Davies, P., Haber, P., and Whitfield, J. B. 2003. Traditional markers of excessive alcohol abuse. Addiction 98: (Suppl. 2) 31-43.
Eriksson, C. J. Peter. 2001. The role of acetaldehyde in the action of alcohol (Update 2000). Alcoholism: Clin. Exp. Res. 25 (5): 15S-32S.
Crabb, D. W. 1999. Pathogenesis of alcoholic liver disease: newer mechanisms of injury. Keio. J. Med. 48:184-188.
Dianzani, M. U. 1985. Lipid peroxidation in ethanol poisoning: A critical reconsideration. Alcohol Alcohol 20:161-173.
Esterbauer, H. 1985. Lipid peroxidation products: formation, chemical properties and biological activities. In: Poli, G., Cheeseman, K. H., Dianzani, M. U., and Slater, T. F. (eds.), Free radicals in liver injury. IRL Press, Oxford pp. 29-34.
Fink, R., Marjot, D. H., Cawood, P., Norden, A. G., Iversen, S. A., and Dormandy, T. L. 1985. Increased free-radical activity in alcoholics. Lancet 2:291-294.
Franke, L., and Porstmann, T. 1994. A highly sentitive non-radioactive cytotoxicity assay for human target cells. J. Immunol. Mehtods 171:259-262.
French, S. W. 1993. Nutrition in the pathogenesis of alcohol liver disease. Alcohol Alcohol 28:97-109.
Gloria, L., Cravo, M., Camilo, M. E., Resende, M., Cardoso, J. N., Oliveira, A. G., Leitao, C. N., and Mira, F. C. 1997. Nutritional deficiencies in chronic alcoholics: relation to dietary intake and alcohol consumption. Am. J. Gastroenterol. 92: 485-489.
Hawkins, R., and Kalant, H. 1972. The metabolism of ethanol and its metabolic effects. Pharmacol. Rev. 24, 67-138.
Hwu, H. G., Yeh, E. K., and Yeh, Y. L. 1988. Alcoholism by Chinese diagnostic interview schedule: A prevalence and validity study. Acta Psychiatr. Scan. 77: 7-13.
Jagannathan, R., Husain, K., and Somani, S. M. 2001. Interaction of pyridostigmine and physical stress on antioxidant defense system in skeletal muscle of mice. J. Appl. Toxicol. 21: 341-348.
Jentzsch, A. M., Bachmann, H., Fürst, P., and Biesalski, H. K. 1996. Improved analysis of malondialdehyde in human body fluids. Free Radic. Biol. Med. 20: 251-256.
Kuo, C. J., Pan, C. H., Chen, C. C., and Hu, W. H. 1998. Mortality among acute psychiatry in patients before and after the Mental Health Act. Taiwan J. Psychiatry. 12: 532-534.
Kurose, I., Higuchi, H., Kato. S., Miura, S., and Ishii, H. 1996. Ethanol-induced oxidative stress in the liver. Alcoholism: Clin. Exp. Res. 20: 77A-85A.
Lecomte, E., Herberth, B., Pirollet, P., Chancerelle, Y., Arnaud, J., Musse, N., Paille, F., Siest, G., and Artur, Y. 1994. Effect of alcohol consumption on blood antioxidants nutrients and oxidative stress indicators. Am. J. Clin. Nutr. 60: 255-261.
Li, T. K. 1983. The absorption, distribution, and metabolism of ethanol and its effects on nutrition and hepatic function. In: Medical and social aspects of alcohol abuse, 47-77.
Lieber, C. S. 1984. Alcohol and the liver: 1984 update. Hepatology 4, 11243-11260.
Lieber, C. S. 2001. Liver diseases by alcohol and hepatitis C: early detection and new insights in pathogeneses lead to improved treatment. Am. J. Addict. 10 (Suppl): 29-50.
Lieber, C. S. 1987. Microsomal ethanol-oxidizing system. Enzyme 37, 145-56.
Lurdes, M., Luisa, M., Luisa, B., and Manso, C. F. 1995. Evidence for free radical generation due to NADH oxidation by aldehyde oxidase during ethanol metabolism. Archives of Biochemistry and Biophysics 318 (1), April 1: 53-58.
Mantle, D., and Preedy, V. R. 1999. Free radicals as mediators of alcohol toxicity. Adverse Drug React. Toxicol. Rev. 18: 235-252.
Marotta, F., Reizakovic, I., Tajiri, H., Safran, P., and Ideo, G. 1997. Abstinence-induced oxidative stress in moderate drinking is improved by bionormalizer. Hepatogastroenterology 44: 1360-1366.
Nemesánszky, E., Lott, J. A., and Arato, M. 1988. Changes in serum enzymes in moderate drinkings after an alcohol challenge. Clin. Chem. 34: 525-527.
Nordmann, R. 1994. Alcohol and antioxidant systems. Alcohol Alcohol 29: 513-522.
Ojesjo, L., Hagnell, O., and Otterbeck, L. 1998. Motrality in alcoholism among men in the Lundby community Cohort, Sweden: a forty-year follow-up. J. Stud Alcohol 59: 140-145.
Onni, N., Seppo, P., Markku, P., Yuji, I., Blair, B., and Ronald, G. T. 1999. Alcoholism: Clin. Exp. Res. 22 (9): 2118-2124.
Pár Alajos dr., Röth Erzsébet dr., Rumi Gyöegy jr dr., Kovács Zoltán dr., Nemes János dr., és Mózsik Gyula dr. 2000. Oxidatív atressz és antioxidáns védelem alkoholos májbetegségben és krónikus C hepatitisben. Orvosi Hetilap 141 (30): 1655-1659.
Patricia, E. G., Barton, Y. W., Shawn, K., Rosie, A. S., Charles, B. C., and Robert, A. R. 2001. Involvement of cyclooxygenase-2 in the potentiation of allyl alcohol-induced liver injury by bacterial lipopolysaccharide. Toxicol. Appl. Pharmacol. 174: 113-121.
Rin, H., and Lin, T. Y. 1962. Mental illness among Formosan aborigines as compared with the Chinese in Taiwan. J. Ment. Sci. 108: 134-146.
Rosalki, S. B., Rau, D., Lehmann, D., and Prentice, M. 1970. Determination of serum gama-glutamyl transpeptidase activity and its clinical applications. Ann. Clin. Biochem. 7: 143-147.
Schuckit, M. A. 1995. Alcohol and alcoholism. In: Braunwald, E., Isselbacher, K. J., eds. Harrison’s principles of internal medicine, 13th ed. New York: McGraw-Hill, pp. 2420-2425.
Shaper, A. G. 1990. Alcohol and mortality: a review of prospective studies, Brit. J. Addiction 85: 837-847.
Shen, C. Y., Lee, H. S., Hsuang, L. C., Tsai, K. S., Chen, D. S., and Cheng, A. T. 1996. Alcoholism, hepatitis B and C viral infection, and impaired liver function among Taiwanese Aboriginal groups. Am. J. Epidemiol. 143: 936-942.
Stephen, S., David, J., and Chris, P. D. 2001. Alcoholic liver disease: new insights into mechanisms and preventative strategies. Trends in Mol. Med. 7 (9): 408-413.
Suematsu, T., Matsumura, T., Sato, N., Miyamoto, T., Ooka, T., Kamada, T., and Abe, H. 1981. Lipid peroxidation in alcoholic liver disease in humans. Alcoholism: Clin. Exp. Res. 5: 427-430.
Suzuki, K., Koike, H., Matsui, H., Ono, Y., Hasumi, M., Nakazato, H., Okugi, H., Sekine, Y., Oki, K., Ito, K., Yamamoto, T., Fukabori, Y., Kurokawa, K., and Yamanaka, H. 2002. Gennistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCAP and PC-3. Int. J. Cancer 99: 846-852.
Takeshita, T., Yang, X., Inoue, Y., Sato, S., and Morimoto, K. 2000. Relationship between alcohol drinking, ADH2 and ALDH2 genotypes, and risk for hepatocellular carcinoma in Japanese. Cancer Lett. 149: 69-76.
Tanaka, F., Shiratori, Y., Yokosuka, O., Imazeki, Y., and Omata, M. 1997. Polymorphyisms of alcohol-metabolizing genes affects drinking behavior and alcoholic liver disease in Japanese men. Alcoholism: Clin. Exp. Res. 21: 596-601.
Wang, S., Phelan, S. A., Forsman-Semb, K., Taylor, E. F., Petros, C., Brown, A., Lerner, C. P., and Paigen, B. 2003. Mice with Targeted Mutation of Peroxiredoxin 6 Develop Normally but Are Susceptible to Oxidative Stress. J. Biol. Chem. 278: 25179-25190.
Whitfield, J. B. 2001. Gama glutamyl transferase. Crit. Rev. Clin. Lab. Sci. 38: 263-355.
Yang, H. I., Lu, S. N., Liaw, Y. F., You, S. L., Sun, C. A., Wang, L. Y., Hsiao, C. K., Chen, P. J., Chen, D. S., and Chen, C. J. 2002. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N. Engl. J. Med. 347: 168-74.
Yokoyama, A., Muramatsu, T., Omori, T., Matsushita, S., Yoshimizu, H., Higuchi, S., Yokoyama, T., Maruyama, K., Ishii, H. 1999. Alcohol and aldehyde dehydrogenase gene polymorphsims influence susceptibility to esophageal cancer in Japanese alcoholics. Alcoholism: Clin. Exp. Res. 23: 1705-1710.


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