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http://dx.doi.org/10.3831/KPI.2010.13.4.005

Study of four week repeated dose toxic test of Sweet Bee Venom in Beagle Dogs  

Park, Jae-Seuk (Dept. of Acupuncture & Moxibustion, Oriental Medical College, Sangji University)
Lee, Kwang-Ho (Dept. of Acupuncture & Moxibustion, Oriental Medical College, Sangji University)
Kwon, Ki-Rok (Dept. of Acupuncture & Moxibustion, Oriental Medical College, Sangji University)
Publication Information
Journal of Pharmacopuncture / v.13, no.4, 2010 , pp. 5-41 More about this Journal
Abstract
Objectives: This study was performed to analyse four week repeated dose toxicity of Sweet Bee Venom(Sweet BV) extracted from the bee venom in Beagle dogs. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP) at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of four week repeated dose toxicity of Sweet BV which was administered at the level of 0.56mg/kg body weight which is eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14mg/kg as midium and low dosage, respectively. Equal amount of excipient(normal saline) to the Sweet BV experiment groups was administered as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups were appealed pain sense in the treating time compared to the control group, and hyperemia and movement disorder were observed around the area of administration in all experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. In the urine analysis, CBC and biochemistry didn't show any significant changes in the experiment groups compared with control group. 5. For weight measurement of organs, experiment groups didn't show any significant changes compared with control group. 6. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, cerebrum, liver, lung, kidney, and spinal cords were removed and conducted histologocal observation with H-E staining. In the histologocal observation of thigh muscle, cell infiltration, inflammatory, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes were depend on the dose of Sweet BV. But another organs were not detected in any abnormalities. 7. The proper high dosage of Sweet BV for the thirteen week repeated test in Beagle dogs may be 0.28mg/kg in one time. Conclusion: Above findings suggest that Sweet BV is relatively safe treatment medium. Further studies on the subject should be conducted to yield more concrete evidences.
Keywords
Sweet Bee Venom; melittin; four week repeated dose toxicity; Beagle dog;
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Times Cited By KSCI : 11  (Citation Analysis)
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1 Kwon KR, Choi SH, Cha BC. Component Analysis of Sweet BV and Clinical Trial on Antibody Titer and Allergic Reactions. Journal of Korean Pharmacopuncture Institute. 2006; 9(2): 79-86.   과학기술학회마을   DOI   ScienceOn
2 Renata MS, Jorge A, Hugo V. Structural and functional behavior of biologically active monomeric melittin. J Molecular Graphics and Modelling. 2007; 25: 767-772.   DOI   ScienceOn
3 Lee JS, Lee JY, Kwon KR, Lee HC. A Study on Allergic response between Bee Venom and Sweet Bee venom Pharmacopunture. Journal of Korean Pharmacopuncture Institute. 2006; 9(3): 61-77.   과학기술학회마을   DOI   ScienceOn
4 Lind DS, Hochwald SN, Malaty J, Rekkas S, Mishra G, et al. nuclear factor-${\kappa}B$ is upregulated in colorectal cancer. Surgery. 2001; 130: 363-369.   DOI   ScienceOn
5 Aranha MM. $NF-{\kappa}B$ and apotosis in colorectal tumorigenesis. Eur J Clin Invest. 2007; 37: 416-424.   DOI   ScienceOn
6 Park HJ, Lee HJ, Choi MS, Son DJ, Song HS, Song MJ, et al. JNK pathway is involved on the inhibition of inflammatory target gene expression and $NF-{\kappa}B$ activation by melittin. J. Inflammation. 2008; 5(7): 1-13.   DOI   ScienceOn
7 Kim YJ, Lim CS, Kwon KR. Study of single dose toxic test of Sweet Bee Venom in rats. Journal of Korean Pharmacopuncture Institute. 2009; 12(4). 5-32.   과학기술학회마을   DOI   ScienceOn
8 식품의약품안정청. 식품의약품안전청고시 제2008-56호.
9 이상인. 본초학. 수서원. 1985; 4-5.
10 Kang KS, Kwon KR. Clinical Studies on 5 Cases of Multiple Sclerosis by Acupuncture Therapies. The Journal of Korean Acupuncture & Moxibustion Society. 2003; 20(1) : 209-217.
11 Kwon KR. Clinical Studies of Amyotrophic Lateral Sclerosis(ALS) through Korean Medicine. The Journal of Korean Acupuncture & Moxibustion Society. 2003; 20(3) : 209-216.
12 Lee JS, An CS, Kwon KR. A Clinical Study on the case of Fascioscapulohumeral (FSH) Muscular Dystrophy Treated with Traditional Korean Medicine. The Journal of Korean Acupuncture & Moxibustion Society. 2001; 18(3) : 227-238.
13 Kwon KR, Chu CS, Park HS, Kim MK, Cha BC, Lee E. Experimental studies of quantitative evalution using HPLC and safety of Sweet Bee Venom. Journal of Korean Pharmacopuncture Institute. 2007; 10(2): 81-86.   과학기술학회마을   DOI   ScienceOn
14 Hwang YJ, Lee BC. Clinical Study of Anaphylaxis on Bee-Venom Acupuncture. The Journal of Korean Acupuncture & Moxibustion Society. 2000 ; 17(4) : 149-159.
15 Youn HM. The Clinical Observation of Anaphylaxis on Bee-Venom Acupuncture. The Journal of Korean Acupuncture & Moxibustion Society. 2005 ; 22(4) : 179-188.   과학기술학회마을
16 Robert L, Ronald D, William S. Allergy, Hypersensitivity, Anaphylaxis. Emergency Medicine. Mosby Year Book. 1998; 2759-2766.
17 Kin KU, Seo BM, Yun JS, Lee YK, Choi SH, Lee KM, Lim SC, Seo JC, Jung TY, Han SW. The Comparison of Bee Venom Herbalacupuncture Therapy between Neighboring Acupuncture Points and Neighboring-Remote Acupuncture Points on the Treatment of Lumbar Spine Herniation of Nucleus Pulpous. The Journal of Korean Acupuncture & Moxibustion Society. 2005 ; 22(6) : 181-187.   과학기술학회마을
18 Lee KM, Lee KS, Yem SC, Jang JH, Yun JY, Hwang BC, Kug YS, Jang JY, Choi JS, Kim YJ, Park JU. A Clinical study of Bee-venom acupuncture treatment on protrusion disc Patients. The Journal of Korean Acupuncture & Moxibustion Society. 2004 ; 21(5) : 13-25.
19 Jun HJ, Hwang U, Kim JS, Nam SS, Kim YS. Clinical Evaluation of Herniation of nucleus purposus patients treated by Bee venom therapy. The Journal of Korean Acupuncture & Moxibustion Society. 2003 ; 20(5) : 63-72.
20 Lee DY, Lee KM, Yeom SC, Kim DH, Kim DJ. A Clinical Study of Bee Venom Acupuncture Therapy on Shoulder Pain Patients in Stroke Sequelae. The Journal of Korean Acupuncture & Moxibustion Society. 2006 ; 23(4) : 69-80.   과학기술학회마을
21 Park HJ, Lee SH, Son DJ, Oh KW, Kim KH, Song HS, et al. Antiarthritic effect of Bee Venom. Arthritis & Rheumatism. 2004; 50(11): 3504-3515.   DOI   ScienceOn
22 Jeoung KS, Kim SH, Park SK, Lim HJ, Yoon HS, Ahn HJ. Clinical Study on the Effect of Bee Venom Acupuncture Therapy on the Poststroke Pain. The Journal of Korean Acupuncture & Moxibustion Society. 2005 ; 22(3) : 69-75.
23 Choi YC, Kwon KR, Choi SH. Purification of Peptide Components including Melittin from Bee Venom using gel filtration chromatography and propionic acid/urea polyacrylamide gel electrophoresis. Journal of Korean Pharmacopuncture Institute. 2006; 9(2): 105-112.   과학기술학회마을   DOI   ScienceOn
24 Barbara & Rudolf. Chemistry and Pharmacology of Honey Bee venom. Academic Press. 1986; 329-402.
25 Ko HK. Experimental Studies on the Effect of Bee Venom Theraphy on the Analgesic, Antipyretic and Anti-inflammatory Action. Korean Journal of Oriental Medicine. 1992 ; 13(1):283-292.
26 Kwon KR, Koh HK, Kim YS, Park YB, Kim CH, Kang SK, The Effect of Bee Venom Aqua-acupuncture on the Antitumor and Immune Response in the Epithelioma by 3-MCA. The Journal of Korean Acupuncture & Moxibustion Society. 1997 ; 14(2) : 151-172.   과학기술학회마을
27 Lee SN, Hong SY, Jo HC, Byeon IJ, Song HS,. Kim GH, The Clinical Study on Bee Venom Acupuncture Treatment on Osteoarthritis of Knee Joint. The Journal of Korean Acupuncture & Moxibustion Society. 2003 ; 20(5) : 73-8.
28 Wang WH, Ahn KB, Lim JK, Jang HS, Clincal Investigation Compared with the Effects of the Bee Venom-Acupuncture on Knee Joint with Osteoarthritis. The Journal of Korean Acupuncture & Moxibustion Society. 2001 ; 18(3) : 35-47.
29 Lee SH, Lee HJ, Baek YH, Kim SY, Park JK, Hong SJ, Yang HI, Kim KS, Lee JD, Choi DY, Lee DI. Effects of Bee Venom on the pain, edema, and acute inflammatory reactant of Rheumatoid Arthritis patients. The Journal of Korean Acupuncture & Moxibustion Society. 2003 ; 20(2) : 77-84.
30 Kim TH. Kang KS, Kwon KR. Three cases of affections of the hip treated with Korean Bee-Venom therapy. Journal of Korean Pharmacopuncture Institute. 2001; 4(3): 122-130.   과학기술학회마을   DOI   ScienceOn
31 Lee SH, Hong SJ, Kim SY, Yang HI, Lee JD, Choi DY, Lee DI, Lee YH. Randomized Controlled Double Blind Study of Bee Venom Therapy on Rheumatoid Arthritis. The Journal of Korean Acupuncture & Moxibustion Society. 2003 ; 20(6) : 80-88.
32 Academic committee of KPI. Pharmacopuncturology. Elsevier Korea. 2008; 3, 167-199.
33 김양강. 독성학. 동화기술. 1984; 15-18.
34 허인회. 독성학. 신일상사. 1993; 9-10, 185-186.
35 식품의약품안정청. 식품의약품안전청고시 제2005-60호.
36 Kwon KR, Koh HK. An Experimental Study with Bee Venom Therapy on Anti-inflammatory and Analgesic Effects. The Journal of Korean Acupuncture & Moxibustion Society. 1998 ; 15(2) : 97-103.   과학기술학회마을