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

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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The Hepatotoxicity and the Effect of Antioxidative Vitamins by the Simultaneous Administration of Caffeine and Acetaminophen in vitro

Caffeine과 Acetaminophen으로 인한 간독성과 항산화성 비타민의 효과

  • 노숙령 (중양대학교 식품영양학과) ;
  • 옥현이 (중양대학교 식품영양학과) ;
  • 이재관 (중앙대학교 생물공학과)
  • Published : 1997.12.01
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Abstract

Hepatotoxicity of caffeine and acetaminophen was investigated in this study. Special attention was paid to the effect of vitamins on the reduction of hepatotoxicity caused by the chemicals. Rat hepaocytes isolated by two-step perfusion method were cultured in two differents methods-suspension, monolayer cultures-, and exposed to caffeine and/or acetaminophen for 24hrs. Caffeine or acetaminophen exhibited no significant hepatotoxicity in terms of intracellular glutathione(GSH) level and lipid peroxidation(MDA), but GSH level was significantly decreased after administrated acetaminophen, and the toxicity caused by the chemicals showed a dose-dependent manner. The synergistic effect of caffeine and acetaminophen was observed when both caffeine and acetaminophen were supplemented to culture medium. At the concentration 1mM, caffeine enhanced the intracellular GSH depletion and MDA formation by 63% and 64%, respectively, compared to single supplementation of 10mM acetaminophen in culture medium. This hepatotoxicity induced membrane integrity loss was observed by lightmicroscope on the simultaneous administration of caffeine and acetaminophen in monolayer cultured hepatocytes. Co-supplementation of vitamins with caffeine/acetaminophen to culture medium results in the protection of hepatocytes from hepatotoxic attach by caffeine/acetaminophen. Especially, vitamin E was superior to vitamin C and $\beta$-carotene from the standpoints of GSH depletion and MDA formation. From this results, it has been speculated that vitamin E may play a role of antioxidant scavenging radicals produced from acetaminophen. Taken all together, in vitro culture system like monolayer culture of hepatocytes may be a useful tool for the evaluation of hepatotoxicity or protection ability of food ingredients.

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References

  1. 산업 생산 연보 경제기획원 조사통계국
  2. 도시 가계 연보 경제기획원 조사통계국
  3. Diet and drug interactions Intolerance to intentional additives Roe, D. A.
  4. Ann Intern. Med v.87 Acetaminophen Ameer, B.;Greenblatt, D. J.
  5. Modern nutrition in health and disease(7th ed.) Diet nutrition and drug reaction Roe, D. A.
  6. Lancet v.1 Hepatic damage and death from overdosage of paracetamol Clark, R.;Thompson, R. P. H.;Borirakchanyavat, V.;Widdop, B.;Davidson, A. R.;Gulding, R;Williams, R.
  7. J. Pharm. Exp. Therapeu. v.248 Mechanism of increased hepatotoxicity of acetaminophen by the simultaneous administration on caffeine in the rat Sato, C.;Izumi, N.
  8. J. Toxi-col. v.34 Increased hepatotoxicity of acetaminophen by con-comitant administration of caffcine in the rat Sato, C.;Izumi, N.;Nouch, J.;Hasumura, Y.;Takeuch, J.
  9. J. Pharm Exp. Therapeu. v.252 Effect of methylxanthines on acetaminophen hepatotoxicity in various induction states Kalhorn, T. F.;Lee, C. A.;Slattery, J. T.;Nelson, S. D.
  10. Biochem. Pharmacol v.46 Interaction of caffeine with acetaminophen Jawm S.;Jeffery, E H.
  11. N Engl. J. Med. v.333 Drug-mduced hepatotoxicity Lee, W. M.
  12. Mol. Pharmacol. v.28 Mechanisms of N-acctyl-p-benzo-quinone imine cytotoxicity Albano, E.;Rundgren, M.;harvison, P J.;Nelson, S D.;Moldeus, P.
  13. Biochem. Pharmacol. v.27 Paracetamol metabolism and toxicity in isolated hepatocytes from rat and mouse Moldeus, P.
  14. Relation to toxicity Biochem Biophys. Res. Commun. v.203 loss of CYP2E1 and CYP1A2 as a function of acetaminophen dose Snawder, J. E.;Roe, A. L.;Benson, R W.;Roberts, D. W.
  15. Biochem. Soc Trans. v.10 Roles and funct-ions of glutathione Cohen, G. M.;Freedman, R B.
  16. Pharmacol Rev v.36 Glutatlnone depletion and susceptibility Reed, D J.;Fariss, M. W.
  17. J. Pharm. Exp. Theropeu v.189 Acetaminophen-induced hepatic necrosis. I.Roles of drug metabolism Mitchell, J. R.;Jollow, D. J.;Potter, W. Z.;Davis, D G.;Gillette, J. R.;Brodie, B. B.
  18. Annu. Rev. Med. v.35 Acetaminophen hepatotoxicity Black, M.
  19. Proc. Natl. Acad. Sci. USA v.81 N-acetyl-p-benzoquinone imine. a cytochrome $P_{450}$-mediated oxidation product of acetaminophen Dahlin, D. C.;Miwa, G. T.;Lu, A. T. H.
  20. J. Korean Soc. Food Nutr. v.23 Lipid peroxidation and its nutritional significance Cheigh, H S
  21. J. Int. Med. Res. v.4 metabolism of paracet-amol after therapeutic and hepatotoxie doses in man Davis, M;Labadarios, D.
  22. J. Korean Soc. Food Nutr. v.80 Changes in free amino acids by lipid deterioration in the bio-logical system of rice bran Song, Y O;Cheigh, H. S.;Pyeun, J. H.
  23. Am. J. Clin Nutr v.57(suppl) Lipid peroxidation: its mechanism, measurement, and significance Halliwell, B.;Sasanna, C
  24. Fd. Chem. Toxic. v.32 Nutrition and health aspects of free ra-dicals and antioxidants Aruama, O. I.
  25. Methods Biol. v.13 Preparation of isolated rat liver cells Seglen, P. O
  26. In Vitro Cell Biol. v.22 Use of low-speed, iso-dcnsity percoll contrifugation method to increase viability of isolated rat liver cells Kreamer, B. L.
  27. Anal. Biochem. v.106 Determination of glutathione and glu-tathione disulfide using. glutathione reductase and 2-venylpyridine Griffith, O. W.
  28. Biochem. Pharmacol. v.49 Oxidative st-ress in isolated rat hepatocytes during naproxen me-chanism Yokoyama, H.;Horie, T.;Awazu, S.
  29. Drugs v.49 Pharmacological rationale for the clmical use of caffeine Sawynok, J.
  30. Biochem Pharmacol. v.37 Caffeine and theophvlline meta-bolism in newbom and adult human hepatocytes Berthou, F.;Ratanasavach, D;Alix, D.;Carlhant, D.;Riche, C.;Guillouzo, A.
  31. Chem. Biol Interact. v.47 Paracetamol-stimulated lipid peroxid-ation in isolated rat and mouse hepatocytes Albano, E.;Poli, G.;Chiarpotto, E.;Baiasi, F.;Dia-nzani, M. U.
  32. Biochem. Biophys. v.267 Peroxidation-dependent and peroxidation-indepedent mechanisms by which acetaminophen kills cultured rat hepatocytes Farber, I. L.;Lconard, T. B;Kyle, M E.;Nakae, D.;Serroni, A.;Robers, S. A.
  33. Food Chem. v.51 Freedical reactions involving coffee Goodman, B. A.;Ghdewell, S N;Deighton, N;Morrice, A. E.
  34. Modern nutrition in health & disease(8th ed.) Vitamin E Farrell, P. M.;Roberts, R. J.;Shils, M E.(ed.);Olson, J A(ed.);Shike, M.(ed.)
  35. Free. Radical Biol Med. v.7 Antioxidant functions of carotenoids Krinsky, N. I.
  36. J Nutr v.119 A review of epidemiology evidence that carotenoide reduce the risk of cancer Ziegler, R. G.
  37. J. Biol. Chem. v.43 Glutathione-ascorbic acid antioxidant system in animals Meister, A
  38. Modern nutrition in health and disease(8th ed.) Vitamin A, retinoids, and carotenoids Olson, J. A;Shils, M. E.(ed.);Olson, J. A.(ed.);Shike, M.(ed.)
  39. Vit-amin E, Acomprehensive treatise Biochemical function MaCay, P. B.;Machlin, L. J.(ed.)
  40. FEBS letters v.159 Protection against lipid peroxidation by a microsornal glutathione-sep-endent labile factor Haenen, G R M. M.lBast, A.
  41. Biochem Pharmacol v.39 Lipid peroxidation and antioxidant system in the liver injury produced by glutathione depleting agents Maellaro, E.;Casini, A. F.;Bello, B. P.;Comporti, M
  42. Am. J. Clin Nutr v.59 Effects of β-carotene supplementation on lipid pero-xidation in humans Allard, J. P.;Royall, D;Kurian, R.;Nuggli, R.
  43. Drug Metab. Dispos v.12 Effect of L-ascorbic acid on acetaminophen-induced hepatotoxicity and covalent Miller, M. G.;Jollow, D. J.
  44. J. Food Safety v.4 The pharmacology and toxicology of caffeine Lachance, M. P.
  45. Biochem. Pharmacol v.38 Proteinthiol depletion and killing of cultured hepatocytes by hydrogen peroxide Kyle, M. E.;Nakae, D;Sakaida, I.;Farber, J. L.
  46. J. Nutr v.3 Effect of dietary caff-eine and theophylline on urinary calcium escretion in the adult rat Whiting, S. J.;Whitney, H. L.
  47. Biochem. Biophys v.198 Caff-eine inhibits agonists-mduced cytoplasmic Ca² osci-llations in single rat hepations in single rat hepatocytes Sanchez-Bueno, A.;Marreno, I.;Cobbold, D. H.