한국식품과학회지 (Korean Journal of Food Science and Technology)

한국식품과학회 (Korean Society of Food Science and Technology)
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생약재 추출물의 nicotine 및 dioxin 해독효과

Detoxicating Effects of Oriental Herb Extract Mixtures on Nicotine and Dioxin

  • Park, Ki-Moon (Faculty of Life Science and Technology, Sungkyunkwan University) ;
  • Hwang, Jin-Kook (Faculty of Life Science and Technology, Sungkyunkwan University) ;
  • Shin, Kyoung-Min (Faculty of Life Science and Technology, Sungkyunkwan University) ;
  • Kim, Hyun-Suck (SungkyunBiotech Co.) ;
  • Song, Jae-Hwan (Faculty of Life Science and Technology, Sungkyunkwan University)
  • 발행 : 2003.10.01
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초록

삼백초 및 포공령, 흑두, 금은화, 결명자, 감초 추출은 혼합물(Oriental herb extracts mixture, OHEM) 의 해독효과를 확인하고자 nicotine 및 dioxin에 대한 급성독성시험을 하였다. 치사량(42mg/kg)의 nicotine을 ICR mouse에 복강주사 하였을 때 OHEM 투여군은 대조군에 비해 마비 개시시간이 2배 이상 지연되었으며, 발작 지속 시간은 1/2로 감소하였고 생존율은 73%로 나타나 해독효과가 강한 것으로 밝혀졌다. 인체를 대상으로 nicotine분해 물질인 뇨중 cotinine배설량을 측정한 결과 OHEM의 섭취가 혈 중 nicotine 분해를 촉진시켜 초기 뇨 중 cotinine 배설량을 1.5배까지 증가시킨 후 뇨중 continine 함량을 OHEM 섭취전의 5% 이하로 감소시켰다. TCDD로 급성특성을 유도한 rat 혈액의 임상 화학적 지수에 hemoglobin의 경우 OHEM의 섭취가 TCDD 투여에 따른 감소를 완화시키는 것으로 나타났으며, 혈소판의 경우 TCDD에 의한 감소를 OHEM 투여가 정상수준으로 회복시켰다(p<0.05) Neutrophil seg(%) 및 monocyte(%)은 TCDD 투여로 감소하였으나 OHEM의 투여로 정상수준으로 회복되었다, 알부민 함량은 TCDD 투여에 의해 감소(p<0.05) 하였으나, OHEM투여로 정상 수치로 회복하였으며 또한, GOT 및 GPT활성 역시 TCDD 투여로 증가하였으나. OHEM 투여로 활성을 저하시키는 것으로 나타났다. 총콜레스테롤 및 혈중 중성지질 함량은 TCDD 투여군 모두 유의적으로 증가 하였으며, OHEM의 투여가 TCDD에 의한 총 콜레스테롤 및 중성지질 수준을 유의차 있게 회복시켰다(p<0.05). 신장 기능에 관련된 creatinine은 OHEM 투여에 의해 TCDD에 의한 증가를 억제하였으며 철 함량은 TCDD 투여로 유의차 있게 감소하였으나 OHEM 투여로 정상 수준으로 회복되었다 TCDD 투여는 혈액과 췌장에 대한 독성작용이 간, 신장 및 심장에 대만 작용에 비해 훨씬 강하게 나타났으며, OHEM에 의한 독성 경감작용은 간 및 췌장에서 효과적으로 나타났다. OHEM의 투여가 TCDD에 의한 임상 지수의 변화를 정상수지에 가깝게 회복 시키는 것으로 나타나 체내대사 및 기능장애를 일부 회복시키는 물질임을 확인할 수 있었다.

In this report, we investigated the detoxication effects of Saururus chinenis, Geranium nepalense, Lonicera japonica, Cassia obtusifolia, Glycyrrhiza uralensis, or their mixtures by employing acute toxicity tests for nicotine and dioxin. When fatal doses $(LD_{100}\;=\;42\;mg/kg)$ of nicotine were injected into the abdominal cavities of ICR mice, those treated with OHEM showed delayed paralysis, half the duration of hyperactivity, and a 73 % survival rate. The results revealed the strong detoxicating effects of the mixtures. We also measured the amount of the degradation product of nicotine and cotinine in humans. Consumption of OHEM promoted (he more specific) the metabolic pathways of nicotine, increasing continine excretion by 1.5 times. As a result the amount of cotinine in urine was reduced to less than 5% after treatment with OHEM. In order to test the toxicity of dioxin, we used TcnN(SD)BR rats exposed to TCDD. While TCDD treatment reduced the blood levels of hemoglobin and platelet, OHEM consumption relieved these effects and, furthermore, helped to recover the number of platelet to the normal level (p<0.05). Moreover, neutrophils (%) and monocytes (%), which were reduced by the injection of TCDD, recovered to normal levels upon treatment with OHEM. The amount albumin reduced by TCDD (p<0.05) normalized, while the activities of GOT and GTP increased by TCDD were reduced. Increases in total cholesterol and neutral fatty acids induced by TCDD were also reduced by OHEM injection (p<0.05). In the kidney, TCDD-induced rises in creatinine were suppressed by OHEM treatment, while decreases in iron levels from TCDD were raised to normal. The treatment of TCDD had more toxic effects in the blood and pancreas than on the liver, kidney and heart. On the other hand, the detoxication of OHEM had significant effects on the liver and pancreas. The normalization by OHEM of various clinical abnormalities induced by TCDD demonstrates the detoxicating effect of OHEM that ameliorates systemic metabolism not properly functioning.

키워드

참고문헌

  1. Kwon, Y.T. Enviromental contamination and human exposure by dioxin-like compounds. Res. Inst. Eng. Technol. 15: 851-867 (1998)
  2. Brunneman, K.D., Prokopezyk, B., Djordjevic, M.V. and Hoffmann, D. Formation and analysis of tobacco-specific N-nitro samines. J. Natl. Cancer Inst. 89: 868-873 (1996) https://doi.org/10.1093/jnci/89.12.868
  3. Carmella, S.G., Borukhova, A., Akerkar, S.A. and Hecht, S.S. Analysis of human urine for pyridine-N-oxidemetabolites of 4- (methylmtrosamino)-l-(3-pyridyl)-l-butanone, a tobacco-specificlung carcinogen. Cancer Epidemiol. Biomarkers Prev. 6: 113-120 (1997)
  4. Wynder, E.L. and Muscat, J.E. The changing epidemiology of smoking and lung cancer histology. Environ. Health Perspect. 8: 143-148 (1995)
  5. Poland, A. and Knutson, J.C. 2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin and related halogenated aromatic hydrocarbons; examination of the mechanism of toxicology. Ann. Rev. Pharmacol. Toxicol. 22: 517-554 (1982) https://doi.org/10.1146/annurev.pa.22.040182.002505
  6. Safe, S.H. Comparative toxicology and mechanism of action of polychlorinate dibenzo-$\rho$-dioxins and dibenzofurans. Ann. Rev. Phamacol. Toxicol. 26: 371-399 (1986) https://doi.org/10.1146/annurev.pa.26.040186.002103
  7. Gelboin, H.V. Benzo(a)Pyrene metabolism, activation and carcinogenesis: Role and regulation of mixed-function oxidases and felated enzymes. Physiol. Rev. 60: 1107-1166 (1980) https://doi.org/10.1152/physrev.1980.60.4.1107
  8. Chung, F.L. The prevention of lung cancer induced by a tobacco specific carcinogen in rodents by green and black tea. Proc. Soc. Exp. Viol. Med. 220: 244-248 (1999) https://doi.org/10.1046/j.1525-1373.1999.d01-42.x
  9. Fujiki, H., Suganuma, M., Okabe, S., Sueoka, N., Komori, A., Sueoka, E., Kozu, T., Tada, Y., Suga, K., Imai, K. and Nakachi, K. Cancer inhibition by green tea. Mutat. Res. 18: 307-310 (1998)
  10. Kyung, Y.J. and Lee, D.H. Enhanced conversion to cotinine from nicotine by green tea extract. Korean J. Environ. Agric. 19: 147-153 (2000)
  11. Kim, J.H., Lee, D.H., Cho, H.J. and Jeong, J.M. Effects of phyto extract mixture on the nicotine decomposition. J. Food Hyg. Saf. 17: 8-14 (2002)
  12. Kitchin, K.T. and Woods, J.S. 2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin effect on hepatic microsomal cytochromes p448-mediated activities. Toxicol. Appl. Phamacol. 47 : 537-546 (1979) https://doi.org/10.1016/0041-008X(79)90524-6
  13. Mohammadpour, H., Murray, W.J. and Stohs, S.J. 2,3,7,8-Tetra-chloro-dibenzo-$\rho$-dioxin(2,3,7,8-TCDD)-induced lipid peroxidationin genetically responsive and non-responsive mice. Arch. Environ. Contam. Toxicol. 17: 645-650 (1988) https://doi.org/10.1007/BF01055833
  14. Shin, I.S., Min, K.J. and Kang, H.Y. A study on the preventive effect of extract of GIycyrrhizae Radix and GIycine semen on NAC intoxication. Korean J. Env. Health Soc. 19: 61-68 (1993)
  15. Hong, S.J., Choi, E.G., Lim, H.S., Shon, J.B. and Jeong, S.S. Effect of herbal dentifrice on dental plaque and gingivitis. J. Korean Acad. Dental Health 25: 347-355 (2001)
  16. Lee, S.I. and Ahn, D.K. Traditional Treatment of Oriental Medicine, pp. 970-983. Kyunghee University Press, Seoul, Korea (1994)
  17. Peach, H., Ellard, G.A., Jenner, P.J. and Morris, R.W. A simple inexpensive urine test of smoking. Thorax 40: 351-357 (1985) https://doi.org/10.1136/thx.40.5.351
  18. Statistix. Statistix for Windows. User's Manual. Analytical Software, USA (1996)
  19. Barlow, R.D., Thompson, P.A. and Stone, R.B. Simultaneous determination of nicotine, cotinine and five additional nicotine metabolite in the urine of smokers using pre-colunm derivatisation and HPLC. J. Chromatogr. 419: 375-380 (1987) https://doi.org/10.1016/0378-4347(87)80303-1
  20. Craig, C.R. and Stizel, R.E. Modern Pharmacology. 4th ed. Little Brown,USA (1994)
  21. Kawai, H., Kuroyanagi, M. and Ueno, A. Iridoid glucosides from Lonicera japonica Thunb. Chem. Pharm. Bull. 36: 3664-3666 (1988) https://doi.org/10.1248/cpb.36.3664
  22. Chang, W.C. and Hsu, F.L. Inhibition of platelet activation and endothelial cell injury by polyphenolic compounds isolated from Lonicera japonica Thunb. Prost. Leuk. Essential Fatty Acids 45: 307-312 (1992) https://doi.org/10.1016/0952-3278(92)90088-Z
  23. Trushin, N. and Hecht, S.S. Strereoselective metabolism of nicotine tobacco-specific N-nitrosamines to 4-hydroxy-4-(3-pydidyl) butanoic acid in rats. Chem. Res. Toxicol. 12: 163-171 (1998)
  24. Hwang, S.Y., Kim, S.K., Kim, S.H., Kwak, Y.S. and Jeong, Y.J. Effect of Korean red ginseng on clinical chemical parameters in male guinea pigs exposed acutely to 2,3,7,8-tetrachlorodibenzo-$\rho$-dioxin. J. Korean Soc. Food Sci. Nutr. 28: 1349-1354 (1999)
  25. Brewster, D.W. and Matsumura, F. 2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin reduces lipoprotein lipase activity in the adipose tissue of the guineapig. Biochem. Biophys. Res. Commun. 122: 810-817 (1989)
  26. Kim, W., Hwang, S.Y., Lee, H., Song, H. and Kim, S. Panax ginseng protects the testis against 2,3,7,8-tetrachlorodibenzo-$\rho$-dioxin induced testicular damage in guinea pigs. BJU Int. 83: 842-849 (1999) https://doi.org/10.1046/j.1464-410x.1999.00046.x
  27. Zhang, H.S., Nam, S.H. and Kang, J.K. Protective effects of bear bile against hepatotoxicity induced by 2,3,7,8-tetrachlorodibenzo-$\rho$-dioxin (TCDD) in mice. Korean J. Pharmacogn. 32: 121-127 (2001)
  28. Hwang, S.Y., Yang, J.B., Chang, C.S., Lee, Y.C. and Lee, H.Y. Protective effect of cornu parvum extract on tioxicity induced by 2,3,7,8-tetrachlorodibenzo-$\rho$-dioxin in rat. Korea J. Oriental Physiol. Pathol. 16: 647-679 (2002)
  29. Vecchini, F., Mace, K., Magdalou, J., Mahe, Y., Bernard, B.A. and Shroot, B. Constitutive and inducible expression of drug metabolizing enzymes in cultured human keratinocytes. Br. J. Dermatol. 132: 14-21 (1995) https://doi.org/10.1111/j.1365-2133.1995.tb08618.x