우황청심원의 마우스 단회 경구투여 독성시험 연구
Single-Dose Oral Toxicity Test of Woohwangchungshim-won in Mice
1
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
The object of this study was to obtain acute toxicity information (single-dose oral toxicity) of Woohwangchungshim-won (WHCSW), a pill type herbal medicine used in Korean Medicine (KM) for treating stroke. In order to obtain the 50% lethal dose (LD50), approximate lethal dosage (ALD) and target organs, WHCSW powders were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) ㎎/㎏ (body weight.) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines (Notification No. 2009-116). The mortality and changes in the body weight, clinical signs and gross observation were monitored for 14 days after single-dose oral administration of WHCSW according to KFDA Guidelines with organ weights and histopathological changes were observed in 12 principle organs. After single-dose oral administration of WHCSW, we could not find any mortality and toxicological evidences up to 2,000 ㎎/㎏-administered group, except for some accidental findings and dose-independent increases of body weight gains in female 1,000 and 500 ㎎/㎏-administered female mice. The results obtained in this study suggest that the LD50 and ALD of WHCSW in both female and male mice after single-dose oral administration were considered as over 2,000 ㎎/㎏ because no mortalities were detected up to 2,000 ㎎/㎏ that was the highest dose recommended by KFDA and Organization for Economic Co-Operation and Development (OECD), and can be safely used in clinics.
Abstract
The object of this study was to obtain acute toxicity information (single-dose oral toxicity) of Woohwangchungshim-won (WHCSW), a pill type herbal medicine used in Korean Medicine (KM) for treating stroke. In order to obtain the 50% lethal dose (LD50), approximate lethal dosage (ALD) and target organs, WHCSW powders were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) ㎎/㎏ (body weight.) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines (Notification No. 2009-116). The mortality and changes in the body weight, clinical signs and gross observation were monitored for 14 days after single-dose oral administration of WHCSW according to KFDA Guidelines with organ weights and histopathological changes were observed in 12 principle organs. After single-dose oral administration of WHCSW, we could not find any mortality and toxicological evidences up to 2,000 ㎎/㎏-administered group, except for some accidental findings and dose-independent increases of body weight gains in female 1,000 and 500 ㎎/㎏-administered female mice. The results obtained in this study suggest that the LD50 and ALD of WHCSW in both female and male mice after single-dose oral administration were considered as over 2,000 ㎎/㎏ because no mortalities were detected up to 2,000 ㎎/㎏ that was the highest dose recommended by KFDA and Organization for Economic Co-Operation and Development (OECD), and can be safely used in clinics.
참고문헌 (27)
- Chen, S.W., "Taiping hui min he ji ju fang", pp.81~ (1987), Xuan feng chu ban she
- Heo, J., "Donguibogam", pp.362~ (2007), Nam san dang
- Nam,, S.G., "Experimental Studies on the Effects of Woowhangchungsimwon and Sohaphyangwon", J Kyung-Hee University Medical Center, 6(2), pp.220~223 (1990)
- 이제원, "우황청심원 관련 최근 연구 동향 : 국내 논문에 대한 고찰", 대한한방내과학회지, 31(4), pp.775~791 (2010), 대한한방내과학회
- 김형우, "Microarray 분석법 활용을 통한 뇌출혈 흰쥐에서의 우황청심원 효능 평가", 대한본초학회지, 22(4), pp.253~260 (2007), 대한본초학회
- 황재웅, "牛黃淸心元의 단독투여 및 연속투여에 따른 정상인의 뇌혈관반응도의 비교연구", 대한한의학회지, 30(1), pp.95~108 (2009), 대한한의학회
- Cho, G. S., "The Effects of Woohwangcheongsim-won on Hypoxic E18 Cortical Neuroblast", Korean J Orient Int Med, 22(2), pp.135~144 (2001)
- 박수연, "Effects of p27 Overexpression on Head and Neck Squamous Cell Carcinoma Cell Lines", Anatomy and Cell Biology, 38(3), pp.227~234 (2005), 대한해부학회
- Choi, E. W., "The Comparative examination of pharmacological effects of musk containing and civet containing WooHwangChungSimWon on the hypertension and heart contraction", Korean J Pharmacognosy, 31(3), pp.310~319 (2000)
- 김이동, "牛黃淸心元이 정상인의 血壓, 脈搏數, 腦血流 및 腦血管反應度에 미치는 影響", 대한한방내과학회지, 25(3), pp.440~450 (2004), 대한한방내과학회
- Baek, J. S., "The effect of Woohwangchungsimwon on the learning and memory in NOS inhibitor treated rats in Morris water maze", J Orient Neuropsychiatry, 10(2), pp.115~126 (1999)
- Kwack, S. J., "Comparative Acute Toxicity Studies on Woo Whang Chung Shim Won Suspension and Pill in Mice", Toxicological Research, 12(2), pp.295~303 (1996)
- Kim, H. J., "Hepatotoxicity of Uhwangchungsimwon: Acute and Subacute Studies in Rats", Toxicological Research, 13(3), pp.265~274 (1997)
- Testing Guidelines for Safety Evaluation of Drugs, "Korea Food and Drug Administration(KFDA)", KFDA, ~, pp.Notification No. 2009-116 (2009)
- Organization for Economic Co-Operation and Development, "OECD guideline (423) for testing of chemicals-acute oral toxicity-acute toxic class method", ~ (2001)
- Irwin, S., "Comprehensive observational assessment: Ia. A systemic, quantitative procedure for assessing the behavioral and physiological state of the mouse", Psychopharmacology, 13, pp.222~257 (1968)
- Dourish, C.T., "Experimental Psychopharmacology", pp.325~334 (1987), Humana Press
- Yoon, G.Y., "Dong ui im sang bang je hak", pp.71~ (1985), Myung bo
- Ahn, I.W., "Clinical Study on the Woohwangchungsim-Won (SU-3), Suspension", The New Medical J, 33(2), pp.109~116 (1990)
- Kim, D.W., "Effect of Woohwangchungsimwon on the serum Mercury concentration, blood cells, Liver and Kidney function", J Trad Kor Med, 8(1), pp.37~42 (1998)
- Plata, E.J., "Growth and haematologic properties of the BALB", wm strain of inbred mice, 1972, pp.22(5), 712~720
- Yamaguchi, C., "Effects of room temperature on reproduction, body weight and organ weights, food and water intakes, and hematology in mice", Exp Anim, 32(1), pp.1~11 (1983)
- JaeHyun Lee, "Single Subcutaneous Dose Toxicity of Polycan？, a β-Glucan Originated from Aureobasidium in Mice", Laboratory Animal Research, 21(4), pp.299~305 (2005), 한국실험동물학회
- Hyeung-Sik Lee, "Single Oral Dose Toxicity Study of Water Extractsof Picrorrhiza Rhizoma In ICR Mice", 한국독성학회지, 22(2), pp.117~126 (2006), 한국독성학회
- Banks, W.J., "Applied veterinary histology", pp.506~526 (1986), Williams & Wilkins
- Pineda, M.H., "Veterinary endocrinology and reproduction", pp.303~354 (1989), Lea & Febiger
- Health Effects Test Guidelines OPPTS 870.100, Acute Toxicity Testing Background, "US Environmental Protection Agency", US EPA, ~ (1998)