행인(杏仁)의 랫트 단회 경구 투여 독성시험

Rat Single Oral Dose Toxicity Test of Armeniacae Semen (Including Endocarp)

  • 김세란 (대구한의대학교 한의과대학 내과학교실) ;
  • 이진원 (대구한의대학교 한의과대학 내과학교실) ;
  • 임소연 (대구한의대학교 한의과대학 내과학교실) ;
  • 정유선 (대구한의대학교 한의과대학 내과학교실) ;
  • 최해윤 (대구한의대학교 한의과대학 내과학교실) ;
  • 김종대 (대구한의대학교 한의과대학 내과학교실)
  • Kim, Se-Ran (Dept. of Internal Medicine, College of Oriental Medicine, Dae-Gu Haany University) ;
  • Lee, Jin-Won (Dept. of Internal Medicine, College of Oriental Medicine, Dae-Gu Haany University) ;
  • Lim, So-Yeon (Dept. of Internal Medicine, College of Oriental Medicine, Dae-Gu Haany University) ;
  • Jung, Yu-Sun (Dept. of Internal Medicine, College of Oriental Medicine, Dae-Gu Haany University) ;
  • Choi, Hae-Yun (Dept. of Internal Medicine, College of Oriental Medicine, Dae-Gu Haany University) ;
  • Kim, Jong-Dae (Dept. of Internal Medicine, College of Oriental Medicine, Dae-Gu Haany University)
  • 발행 : 2012.06.30

초록

Objectives : The object of this study was to obtain acute toxicity information (single oral dose toxicity) of Armeniacae Semen (AS), a medicinal herb used for treating constipation and various respiratory diseases, in rats. Methods : In order to observe the $LD_{50}$ (50% lethal dose), approximate lethal dosage (ALD) and target organs, AS aqueous extracts were orally administered once to female and male Sprague Dawley rats at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight). The mortality, changes in the body weight, clinical signs and gross observation were monitored for 14 days after single oral treatment of AS extracts, and the organ weights and histopathological findings of principle organs were observed after sacrifice. Results : After single oral treatment of AS 2,000 and 1,000 mg/kg, all (5/5; 100%) female and male rats died within 30 minutes after treatment, while no mortalities were observed in the female and male rats treated with 500 mg/kg of AS extract. Therefore, $LD_{50}$ in female and male rats was calculated as 741.95 mg/kg. Seizure, loss of locomotion, salivation, increases of respiration and heart-beat were observed after AS extract treatment, which were observed in all rats including the lowest dosage group, 500 mg/kg in the present study. In addition, lung congestion was visible in all mortal rats with AS 2,000 and 1,000 mg/kg, respectively. Conclusions : The results obtained in this study suggest that AS extract ranges in Class III, because the $LD_{50}$ and ALD in both female and male rats were calculated as 741.95 mg/kg and 500~1,000 mg/kg, respectively. However, AS extract should be carefully treated at clinical applications, because salivation, increase of respiration and heart-beat were also observed in the lowest dosage group, 500 mg/kg in the present study.

키워드

참고문헌

  1. 김동현, 김형민, 류종훈, 엄재영, 김상찬, 양재하, 등. 한방약리학. 서울: 신일상사; 2010, p. 328-30.
  2. 김인락, 김호철, 국윤범, 박성주, 박용기, 박지하, 등. 本草學. 서울: 永林社; 2007, p. 512-3.
  3. Do JS, Hwang JK, Seo HJ, Woo WH, Nam SY. Antiasthmatic activity and selective inhibition of type 2 helper T cell response by aqueous extract of semen armeniacae amarum. Immunopharmacol Immunotoxicol 2006;28(2) :213-25. https://doi.org/10.1080/08923970600815253
  4. 황대룡, 강영성, 김성수, 김대한, 신민교, 송호준. 행인의 알레르기 천식 효과에 대한 연구. 대한본초학회지 2003;18(2):201-8.
  5. 김유승, 송춘호. 행인약침이 항알레르기에 미치는 영향. 경락경혈학회지 2007;24(4):151-62.
  6. Yamamoto K, Osaki Y, Kato T, Miyazaki T. Antimutagenic substances in the Armeniacae semen and Persicae semen. Yakugaku Zasshi 1992;112(12):934-9. https://doi.org/10.1248/yakushi1947.112.12_934
  7. Toriyama-Baba H, Iigo M, Asamoto M, Iwahori Y, Park CB, Han BS, et al. Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat multi-organ carcinogenesis model. Jpn J Cancer Res 2001;92(11):1175-83. https://doi.org/10.1111/j.1349-7006.2001.tb02137.x
  8. Yang HY, Chang HK, Lee JW, Kim YS, Kim H, Lee MH, et al. Amygdalin suppresses lipopolysaccharide-induced expressions of cyclooxygenase-2 and inducible nitric oxide synthase in mouse BV2 microglial cells. Neurol Res 2007;29(1):S59-64. https://doi.org/10.1179/016164107X172248
  9. 김영훈, 조우아, 천순주, 장민정, 성지연, 정연숙, 등. 행인의 약용화장품 활성 및 미백 효과에 관한 연구. 한약응용학회지 2007;7(1):35-9.
  10. 김영욱, 송윤경, 임형호. 행인에서 추출한 Amygdalin 이 좌골신경 단열로 신경이 손상된 쥐의 기능 회복 및 중심회백질의 c-Fos 발현에 미치는 영향. 한방재활의학과학회지 2006;16(4):37-47.
  11. 서부일, 박지하. 행인의 독성에 관한 문헌적 고찰. 제한동의학술원논문집 2008;6(1):135-62.
  12. Suchard JR, Wallace KL, Gerkin RD. Acute cyanide toxicity caused by apricot kernel ingestion. Ann Emerg Med 1998;32(6):742-44. https://doi.org/10.1016/S0196-0644(98)70077-0
  13. 심범상, 최승훈, 박재경. 행인 제제의 독성 및 항암효과와 자연살해세포 활성에 미치는 효과. 대한한방종양학회지 2000;6(1):19-28.
  14. 한국식품의약품안전청. 의약품 등의 독성시험 기준. 서울: 한국식품의약품 안전청 고시 제 2009-116호; 2009, p. 1-59.
  15. Organization for Economic Co-Operation and Development (Ed.). OECD guideline (423) for testing of chemicals - acute oral toxicity-acute toxic class method. OECD/OCDE; 2001, p. 1-14.
  16. Irwin S. Comprehensive observational assessment: Ia. A systemic, quantitative procedure for assessing the behavioral and physiological state of the mouse. Psychopharmacology 1968;13(3): 222-57. https://doi.org/10.1007/BF00401402
  17. Dourish CT. Effects of drugs on spontaneous motor activity. In: Experimental Psychopharmacology. Greenshaw AJ and Dourish CT (Ed). Clifton: Humana Press; 1987, p. 325-34.
  18. 도병경, 권훈정, 이동하, 나안희, 최윤주, 이숙연. 가열조리방법을 통한 행인 내 시안화합물의 저감화. 한국식품위생안전성학회지 2007;22(4):395-400.
  19. 김정훈, 강태욱, 박찬봉, 차광재, 안영근. 아미그달린의 투여경로에 따른 면역생물학적 연구. 약학회지 1996;40(2):202-11.
  20. 김옥, 권기록. 행인약침의 급성 아급성 독성실험 및 Sarcoma-180 항암효과에 관한 실험적 연구. 대한약침학회지 2002;5(1):61-79.
  21. Strugala GJ, Stahl R, Elsenhans B, Rauws AG, Forth W. Small-intestinal transfer mechanism of prunasin, the primary metabolite of the cyanogenic glycoside amygdalin. Hum Exp Toxicol 1995;14(11):895-901. https://doi.org/10.1177/096032719501401107
  22. O'Brien B, Quigg C, Leong T. Severe cyanide toxicity from 'vitamin supplements'. Eur J Emerg Med 2005;12(5):257-8. https://doi.org/10.1097/00063110-200510000-00014
  23. Fox JG, Cohen BJ, Loew FM. Laboratory animal medicine. Orlando: Academic Press. Inc.; 1984, p. 613-8.
  24. Tajima Y (Ed). Biological reference data book on experimental animals. Tokyo: Soft Science Inc.; 1989, p. 1-10.
  25. Yoon HS, Shin YK, Jung YM, Lee HS, Ku SK. Single oral dose toxicity test of low molecular weight fucoidan in rats. Biomol Ther 2009;17(3):325-31. https://doi.org/10.4062/biomolther.2009.17.3.325
  26. Yoon HS, Shin YK, Lee SH, Lee DS, Jung YM, Lee HS, et al. 14 days repeat oral dose toxicity of low molecular weight fucoidan in rats. Biomol Ther 2010;18(1):111-21. https://doi.org/10.4062/biomolther.2010.18.1.111
  27. Banks WJ. Female reproductive system. In: Banks WJ (Ed). Applied veterinary histology. 2nd ed. Baltimore: Williams & Wilkins; 1986, p. 506-26.
  28. Pineda MH. Female reproductive system. In: McDonald LE and Pineda MH (Eds). Veterinary endocrinology and reproduction. Philadelphia: Lea & Febiger; 1989, p. 303-54.
  29. US Environmental Protection Agency. Health Effects Test Guidelines OPPTS 870.1000 Acute Toxicity Testing Background. US EPA August. Washington, DC; 1998, p. 1-6.
  30. Liang AH, Nie SQ, Xue BY, Li GQ, Li ZL. Effects of processing on special toxicity and pharmacodynamics in semen Armeniacae amarum. Zhongguo Zhong Yao Za Zhi 1993;18(8):474-8,
  31. 서부일, 신순식. 알기 쉬운 한약 포제학. 대구: 대원당기획출판사; 2007, p. 293-5.
  32. 이성호, 이성민, 임효진, 김두진, 김갑순. 살구씨의 화학적 조성에 관한 연구. 한국식품영양학회지 1992;5(1):1-6.