Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Protective Effect of Theanine on the Acetaminophen-induced Hepatotoxicity

아세트아미노펜에 의해 유도된 간독성 모델에서의 Theanine의 간보호 효과

  • Eu, Jung-Bu (School of Food Science International University of Korea) ;
  • Kim, Sun-Oh (Jeonnam Natural Resources Research Institute) ;
  • Seoung, Tae-Jong (School of Food Science International University of Korea) ;
  • Choi, Sung-Gil (Division of Applied Life Sciences, Graduate School, Institute of Agricultural & Agricultural & Life Sciences, Gyeongsang National University) ;
  • Cho, Sung-Hwaon (Division of Applied Life Sciences, Graduate School, Institute of Agricultural & Agricultural & Life Sciences, Gyeongsang National University) ;
  • Choi, Chul-Yung (Dept. of Pharmaceutical Formulation Engineering, International University of Korea)
  • 우정부 (한국국제대학교 식품과학부) ;
  • 김선오 (전라남도 천연자원연구원) ;
  • 성태종 (한국국제대학교 식품과학부) ;
  • 최성길 (경상대학교 응용생명과학부) ;
  • 조성환 (경상대학교 응용생명과학부) ;
  • 최철웅 (한국국제대학교 제약공학과)
  • Published : 2010.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

The hepatoprotective effects of theanine on acetaminophen (APAP)-induced hepatotoxicity were investigated in vivo and in vitro. The effects of theanine on liver toxicity induced by APAP were assessed by blood biochemical and histopathological analyses. APAP treatment (400 mg/kg) caused severe liver injury in mice as indicated by their significantly elevated plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Pretreatment with theanine for 3 days attenuated the increase in ALT and AST when challenged with APAP. These protective effects of theanine against APAP-induced toxicity were consistent with the results from the histopathological examinations. We next examined the effects of theanine on the GSH concentration in liver plasma. The hepatic GSH level was significantly elevated in a dose-dependent manner by theanine treatment. The results suggest that the protective effects of theanine APAP-induced hapatotoxicity by antioxidative effect and GSH induction, implying that theanine should be considered a potential chemopreventive agent.

아세트아니모펜(APAP)으로 유도된 간독성 모델에 미치는 theanine의 간 보호 작용에 대하여 간 기능 지표효소의 활성 측정, 항산화 및 GSH량 측정, 조직학적 변화 등을 통해 확인하였다. Theanine은 그 자체로 항산화 효과를 보였으며, 과량 투여된 APAP에 의해 발생하는 간조직의 지질과산화의 감소와 GSH가 회복되는 것을 동물실험을 통해 확인할 수 있었다. 또한 지질과산화와 GSH의 감소로 인해 발생한 간세포의 손상이 theanine의 처리 농도에 비례하여 감소하는 것을 간수치 검사와 간조직 검사를 통해 최종 확인하였다. 지금까지 간보호에 효과를 보이는 녹차의 카테킨이 주로 연구되어 왔으나, 본 연구를 통해 녹차의 theanine도 간 보호작용을 알 수 있었다. 이러한 연구 결과는 주 아미노산 성분인 theanine을 강화시킨 기능성 녹차 및 건강기능식품 개발의 기초 자료로 활용 가능할 것으로 사료된다.

Keywords

References

  1. Kim HK. 2004. Current status and prospect of nutraceuticals. Food Ind Nutr 9: 1-14.
  2. Shim CK. 2004. Implementation and policy direction of the Korean health functional food law and its regulations. Food Sci Ind 37: 37-40.
  3. Goto T, Yoshida Y, Amano I, Horie H. 1996. Simultaneous analysis of individual catechins and caffeine in green tea. Foods & Food Ingred J Jpn 170: 46-51.
  4. Graham HN. 1992. Green tea composition, consumption, and polyphenol chemistry. Prev Med 21: 334-350. https://doi.org/10.1016/0091-7435(92)90041-F
  5. Hasegawa R, Chujo T. 1995.　Preventive effects of green tea against liver oxidative DNA damage and hepatotoxicity in rate treated with 2-nitropane. Food Chem Toxicol 33: 961-970. https://doi.org/10.1016/0278-6915(95)00064-9
  6. Ashihara H, Sano H, Crozier A. 2008. Caffeine and related purine alkaloids: biosynthesis, catabolism, function and genetic engineering. Phytochemistry 69: 841-856. https://doi.org/10.1016/j.phytochem.2007.10.029
  7. Friedman M, Mackey BE, Kim HJ, Lee IS, Lee KR, Lee SU, Kozukue E, Kozukue N. 2007. Structure-activity relationships of tea compounds against human cancer cells. J Agric Food Chem 24: 243-253.
  8. Casimir J, Jadot J, Renard M. 1960. Separation and characterization of N-ethyl-$\gamma$-glutamine from Xerocomus badius. Biochim Biophys Acta 39: 462-468. https://doi.org/10.1016/0006-3002(60)90199-2
  9. Crozier A, Yokota T, Jaganath IB, Marks SC, Saltmarsh M, Clifford MN. 2006. Secondary metabolites in fruits, vegetables, beverages and other plant-based dietary components. In Plant Secondary Metabolites. Blackwell, Oxford, England. Chapter 7, p 208-302.
  10. Sakato A. 1949. The chemical constituents of tea. III. A new amide theanine. Nippon Nogeikagaku Kaishi 23: 262-267.
  11. Pacheco GS, Panatto JP, Fagundes DA, Scaini G, Bassani C, Jeremias IC, Rezin GT, Constantino L, Dal-Pizzol F, Streck EL. 2009. Brain creatine kinase activity is inhibited after hepatic failure induced by carbon tetrachloride or acetaminophen. Metab Brain Dis 24: 383-394. https://doi.org/10.1007/s11011-009-9143-8
  12. Guengerich FP, Kim DH, Iwasaki M. 1991. Role of human cytochrome P-450 IIEL in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 4: 168-179. https://doi.org/10.1021/tx00020a008
  13. Imaeda AB, Watanabe A, Sohail MA, Mahmood S, Mohamadnejad M, Sutterwala FS, Flavell RA, Mehal WZ. 2009. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. J Clin Invest 119: 305-314.
  14. Lee WM. 2004. Acetaminophen and the US Acute Liver Failure Study Group: lowering the risks of hepatic failure. Hepatology 40: 6-9. https://doi.org/10.1002/hep.20293
  15. Laine JE, Auriola S, Pasanen M, Juvonen RO. 2009. Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. Xenobiotica 39: 11-21. https://doi.org/10.1080/00498250802512830
  16. Fischer LJ, Green MD, Harman AW. 1986. Levels of acetaminophen and its metabolites in mouse tissue after a toxic dose. J Pharmacol EXP Ther 219: 281-286.
  17. Sun J, Schnackenberg LK, Beger RD. 2009. Studies of acetaminophen and metabolites in urine and their correlations with toxicity using metabolomics. Drug Metab Lett 3: 130-136. https://doi.org/10.2174/187231209789352139
  18. Marchetti A, Rossiter R. 2009. Managing acute acetaminophen poisoning with oral versus intravenous N-acetylcysteine: a provider-perspective cost analysis. J Med Econ 12: 384-391. https://doi.org/10.3111/13696990903435829
  19. Clissold SP. 1986. Pracetamol and phenacetin. Drugs 4: 46-59.
  20. Hinson JA, Roberts DW, James LP. 2010. Mechanisms of acetaminophen-induced liver necrosis. Handb Exp Pharmacol 196: 369-405. https://doi.org/10.1007/978-3-642-00663-0_12
  21. Jaeschke H, Bajt ML. 2006. Intracellular signaling mechanisms of acetaminophen-induced liver cell death. Toxicol Sci 89: 31-41. https://doi.org/10.1093/toxsci/kfi336
  22. Schwabe RF, Uchinami H, Qian T, Bennett BL, Lemasters JJ, Brenner DA. 2004. Differential requirement for c-Jun NH2-terminal kinase in TNF$\alpha$- and Fas-mediated apoptosis in hepatocytes. FASEB J 18: 720-722.
  23. Matsuzaki T, Hata Y. 1985. Antioxidative activity of tea leaf catechins. Nippon Nogeikagaku Kaish 59: 129-134. https://doi.org/10.1271/nogeikagaku1924.59.129
  24. Wang EJ, Li Y, Lin M, Chen L, Stein A, Reuhl KR, Yang CS. 1996. Protective effects of garlic and related organosulfur compounds on acetaminophen-induced hepatotoxicity in mice. Toxicol Appl Pharmacol 136: 146-154. https://doi.org/10.1006/taap.1996.0018
  25. Wu YL, Piao DM, Han XH, Nan JX. 2008. Protective effects of salidroside against acetaminophen-induced toxicity in mice. Biol Pharm Bull 31: 1523-1529. https://doi.org/10.1248/bpb.31.1523
  26. Yokozawa T, Dong E, Chung HY, Oura H, Nakagawa H. 1997. Inhibitory effect of green tea on injury to a cultured renal epithelial cell line, LLC-PK1. Biosci Biotechnol Biochem 61: 204-206. https://doi.org/10.1271/bbb.61.204
  27. Lee YS, Han OK, Jeon TW, Lee ES, Kim KJ, Park CW, Kim HJ. 2002. Effect of Astrahali radix extract on acetaminophen-induced hepatotoxicity in mice. Korean J Oriental Physiol Pathol 16: 707-713.
  28. Lee KJ, You HJ, Park SJ, Chung YC, Jeong TC, Jeong HG. 2001. Hepatoprotective effects of Platycodon grandiflofum on acetaminophen-induced liver damage in mice. Cancer Lett 174: 73-81. https://doi.org/10.1016/S0304-3835(01)00678-4
  29. Levine RL, Garland D, Oliver CN, Amici A, Climet I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER. 1990. Determination of carbony content in oxidatively modified proteins. Methods Enzymol 186: 464-478. https://doi.org/10.1016/0076-6879(90)86141-H
  30. Sugiyama T, Sadzuka Y. 2004. Theanine, a specific glutamate derivative in green tea, reduces the adverse reactions of doxorubicin by changing the glutathione level. Cancer Lett 212: 177-184. https://doi.org/10.1016/j.canlet.2004.03.040
  31. Yeung JH, Chiu LC, Ooi VE. 1994. Effect of polysaccharide peptide (PSP) on glutathion and protection against paracetamol-induced hepatotoxicity in the rat. Methods Find Exp Clin Pharmacol 16: 723-729.
  32. Biaglow JE, Varnes ME, Roizen-Towle L, Clark EP, Epp ER, Astor MB, Hall EJ. 1986. Biochemistry of reduction of nitro heterocycles. Biochem Pharmacol 35: 77-90. https://doi.org/10.1016/0006-2952(86)90561-7
  33. Vermeulen NPE, Bessems JGM, Van de Straat R. 1992. Molecular aspects of paracetamol-induced hepatotoxicty and its mechanism-based prevention. Drug Metab Rev 24: 367-407. https://doi.org/10.3109/03602539208996298
  34. Cohen SD, Khairallah EA. 1997. Selective protein arylation and acetaminophen-induced hepatotoxicty. Prug Metab Rev 29: 59-101. https://doi.org/10.3109/03602539709037573
  35. Lee KJ, You HJ, Park SJ, Kim YS, Chung YC, Jeong TC, Jeong HG. 2001. Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice. Cancer Lett 174: 73-81. https://doi.org/10.1016/S0304-3835(01)00678-4

Cited by

  1. Effects of Cultured Acer tegmentosum Cell Extract Against Hepatic Injury Induced by D-galactosamine In SD-Rats vol.28, pp.5, 2015, https://doi.org/10.7732/kjpr.2015.28.5.551
  2. Effects of white lotus extracts on sleeping, chloride influx, and oxidation vol.20, pp.4, 2011, https://doi.org/10.1007/s10068-011-0131-5
  3. Effect of Semisulcospira libertina Extract on Hepatic Injury Induced by D-galactosamine vol.36, pp.4, 2018, https://doi.org/10.11626/KJEB.2018.36.4.498
  4. 멀꿀 열매 추출물의 항산화 활성 및 H2O2로 유도된 산화적 스트레스와 아세트아미노펜 독성 모델에서의 간 보호효과 vol.28, pp.6, 2010, https://doi.org/10.5352/jls.2018.28.6.708