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Evaluation of Cytotoxic Properties of Caffeine Treated with Over-the-counter Drugs in the Intestinal Cells

카페인과 일반의약품의 복합처리에 의한 장관계 세포 독성 평가

  • Choi, Hyun-A (Department of Food Science and Technology, College of Natural Science, Seoul Women’s University) ;
  • Kim, Mi-Ri (Department of Food Science and Technology, College of Natural Science, Seoul Women’s University) ;
  • Park, Kyung-A (Department of Food Science and Technology, College of Natural Science, Seoul Women’s University) ;
  • Hong, Jung-Il (Department of Food Science and Technology, College of Natural Science, Seoul Women’s University)
  • 최현아 (서울여자대학교 자연과학대학 식품공학과) ;
  • 김미리 (서울여자대학교 자연과학대학 식품공학과) ;
  • 박경아 (서울여자대학교 자연과학대학 식품공학과) ;
  • 홍정일 (서울여자대학교 자연과학대학 식품공학과)
  • Received : 2012.02.09
  • Accepted : 2012.03.06
  • Published : 2012.06.30

Abstract

Caffeine is a xanthine alkaloid derivative found in many foods and beverages. Dietary caffeine may interact with commonly-consumed over-the-counter (OTC) drugs in body. In this study, cytotoxic effects on the intestinal cells by combined treatment of caffeine with several OTC drugs, including ibuprofen, aspirin, and acetaminophen. Cytotoxic effect of caffeine was more potent in normal intestinal INT 407 cells than in colon cancer HCT 116 cells. Relative toxicity of caffeine and the OTC drugs was significantly enhanced in INT 407 cells when treated together. Intracellular thiol levels of the cells treated with the OTC drugs increased in the presence of caffeine. When HCT 116 cells were incubated with each OTC drug after or before caffeine treatment, the relative cytotoxicity of the OTC drugs increased. The present study may provide basic information about possible health effects through the interactions between caffeine and OTC drugs in the intestinal cells.

다양한 식품 중에 널리 분포되어 있는 생리활성 성분 카페인과 일반의약품 성분 AAP, Asp 및 Ibu와의 혼용 시 상호작용에 의한 세포 독성 변화를 장관계 세포모델에서 조사하였다. 카페인은 정상 장관계 세포 INT 407 및 대장암 세포 HCT 116에 농도의존적인 독성을 나타내었고, $IC_{50}$ 수치는 각각 1.91과 2.45 mM로써 정상세포에 유의적으로 높은 독성을 나타내었다. 카페인과 각각의 약물을 세포에 24시간 동시 처리한 결과 전체적으로 현저한 독성의 변화현상은 발생하지 않았으나, 약물처리 시를 기준으로 한 카페인의 상대적 독성 및 카페인 처리 시를 기준으로 한 약물의 독성이 INT 407 세포에서 유의적으로 증가하였다. 동시 처리 시 약물에 의해 감소된 GSH를 비롯한 thiol성 물질의 세포 내 수준이 카페인 존재 시에 유의적으로 증가하였다. 한편 카페인과 약물을 각각 순서를 달리하여 전후로 처리하였을 때, 특히 HCT 116 세포에서의 약물의 상대적인 독성이 강화되는 현상을 보였다. 일반의약품 AAP, Asp 및 Ibu과 카페인을 다양한 조합에 의해 장관계 세포에 처리하였을 때 일부 상대적인 독성의 강화 또는 약화 현상이 나타났으나 전체적으로 두드러진 독성발현 빛 활성변화는 발견되지 않았다.

Keywords

References

  1. Chou T. Wake up and smell the coffee. Caffeine, coffee, and the medical consequences. Western J. Med. 157: 544-553 (1992)
  2. Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol. Rev. 51: 83-133 (1999)
  3. Davis JM, Zhao Z, Stock HS, Mehl KA, Buggy J, Hand GA. Central nervous system effects of caffeine and adenosine on fatigue. Am. J. Physiol-Reg. I. 284: R399-R404 (2003)
  4. Nehlig A, Daval JL, Debry G. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic, and psychostimulant effects. Brain Res. Rev. 17: 139-170 (1992) https://doi.org/10.1016/0165-0173(92)90012-B
  5. Devasagayam TP, Kamat JP, Mohan H, Kesavan PC. Caffeine as an antioxidant: Inhibition of lipid peroxidation induced by reactive oxygen species. Biochim. Biophys. Acta 1282: 63-70 (1996) https://doi.org/10.1016/0005-2736(96)00040-5
  6. Lu YP, Lou YR, Xie JG, Peng QY, Liao J, Yang CS, Huang MT, Conney AH. Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. P. Natl. Acad. Sci. USA 99: 12455-12460 (2002) https://doi.org/10.1073/pnas.182429899
  7. Hashimoto T, He Z, Ma WY, Schmid PC, Bode AM, Yang CS, Dong Z. Caffeine inhibits cell proliferation by G0/G1 phase arrest in JB6 cells. Cancer Res. 64: 3344-3349 (2004) https://doi.org/10.1158/0008-5472.CAN-03-3453
  8. Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV, Miners JO. Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. J. Pharmacol. Exp. Ther. 265: 401-407 (1993)
  9. Goasduff T, Dreano Y, Guillois B, Menez JF, Berthou F. Induction of liver and kidney CYP1A1/1A2 by caffeine in rat. Biochem. Pharmacol. 52: 1915-1919 (1996) https://doi.org/10.1016/S0006-2952(96)00522-9
  10. Lessenger JE, Feinberg SD. Abuse of prescription and over-thecounter medications. J. Am. Board Family Med. 21: 45-54 (2008) https://doi.org/10.3122/jabfm.2008.01.070071
  11. James LP, Mayeux PR, Hinson JA. Acetaminophen-induced hepatotoxicity. Drug Metab. Dispos. 31: 1499-1506 (2003) https://doi.org/10.1124/dmd.31.12.1499
  12. Mitchell J, Jollow D, Potter W, Davis D, Gillette J, Brodie B. Acetaminophen-induced hepatic necrosis. I. role of drug metabolism. J. Pharmacol. Exp. Ther. 187: 185-194 (1973)
  13. Iqbal N, Ahmad B, Janbaz KH, Gilani AUH, Niazi SK. The effect of caffeine on the pharmacokinetics of acetaminophen in man. Biopharm. Drug Dispos. 16: 481-487 (1995) https://doi.org/10.1002/bdd.2510160606
  14. Renner B, Clarke G, Grattan T, Beisel A, Mueller C, Werner U, Kobal G, Brune K. Caffeine accelerates absorption and enhances the analgesic effect of acetaminophen. J. Clin. Pharmacol. 47: 715-726 (2007) https://doi.org/10.1177/0091270007299762
  15. Choi HA, Kim MR, Hong J. Evaluation of cytotoxic properties of tea polyphenols in intestinal cells treated with over-the-counter drugs. Korean J. Food Sci. Technol. 43: 641-647 (2011) https://doi.org/10.9721/KJFST.2011.43.5.641
  16. Lee BH, Park YS, Kim JS, Yoo JH, Lee JK. Caffeine consumption and its related symptoms in university students. J. Korean Acad. Fam. Med. 28: 9-16 (2007)
  17. Farber E, Rubin H. Cellular adaptation in the origin and development of cancer. Cancer Res. 51: 2751-2761 (1991)
  18. Sato C, Izumi N, Nouchi T, Hasumura Y, Takeuchi J. Increased hepatotoxicity of acetaminophen by concomitant administration of caffeine in the rat. Toxicology 34: 95-101 (1985) https://doi.org/10.1016/0300-483X(85)90159-3
  19. Farag MM, Abdel-Meguid EM. Hepatic glutathione and lipid peroxidation in rats treated with theophylline. Effect of dose and combination with caffeine and acetaminophen. Biochem. Pharmacol. 47: 443-446 (1994)
  20. Poot M, Verkerk A, Koster JF, Jongkind JF. De novo synthesis of glutathione in human fibroblasts during in vitro ageing and in some metabolic diseases as measured by a flow cytometric method. Biochim. Biophys. Acta 883: 580-584 (1986) https://doi.org/10.1016/0304-4165(86)90300-4
  21. Moskaug JO, Carlsen H, Myhrstad MC, Blomhoff R. Polyphenols and glutathione synthesis regulation. Am. J. Clin. Nutr. 81: 277S-283S (2005) https://doi.org/10.1093/ajcn/81.1.277S
  22. Kim BR, Hu R, Keum YS, Hebbar V, Shen G, Nair SS, Kong AN. Effects of glutathione on antioxidant response element-mediated gene expression and apoptosis elicited by sulforaphane. Cancer Res. 63: 7520-7525 (2003)