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

Sweet Bee Venom의 비글견을 이용한 4주 반복 근육시술 독성시험

  • 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)
  • 박재석 (상지대학교 한의과대학 침구학교실) ;
  • 이광호 (상지대학교 한의과대학 침구학교실) ;
  • 권기록 (상지대학교 한의과대학 침구학교실)
  • Received : 2010.08.23
  • Accepted : 2010.11.26
  • Published : 2010.12.30

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

References

  1. 김양강. 독성학. 동화기술. 1984; 15-18.
  2. 허인회. 독성학. 신일상사. 1993; 9-10, 185-186.
  3. 식품의약품안정청. 식품의약품안전청고시 제2005-60호.
  4. Academic committee of KPI. Pharmacopuncturology. Elsevier Korea. 2008; 3, 167-199.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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. https://doi.org/10.3831/KPI.2001.4.3.127
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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. https://doi.org/10.3831/KPI.2006.9.2.105
  19. Barbara & Rudolf. Chemistry and Pharmacology of Honey Bee venom. Academic Press. 1986; 329-402.
  20. 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. https://doi.org/10.1002/art.20626
  21. 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. https://doi.org/10.1186/1476-9255-5-1
  22. 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. https://doi.org/10.3831/KPI.2009.12.4.005
  23. 식품의약품안정청. 식품의약품안전청고시 제2008-56호.
  24. 이상인. 본초학. 수서원. 1985; 4-5.
  25. 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.
  26. Kwon KR. Clinical Studies of Amyotrophic Lateral Sclerosis(ALS) through Korean Medicine. The Journal of Korean Acupuncture & Moxibustion Society. 2003; 20(3) : 209-216.
  27. 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.
  28. Hwang YJ, Lee BC. Clinical Study of Anaphylaxis on Bee-Venom Acupuncture. The Journal of Korean Acupuncture & Moxibustion Society. 2000 ; 17(4) : 149-159.
  29. Youn HM. The Clinical Observation of Anaphylaxis on Bee-Venom Acupuncture. The Journal of Korean Acupuncture & Moxibustion Society. 2005 ; 22(4) : 179-188.
  30. Robert L, Ronald D, William S. Allergy, Hypersensitivity, Anaphylaxis. Emergency Medicine. Mosby Year Book. 1998; 2759-2766.
  31. 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. https://doi.org/10.3831/KPI.2007.10.2.081
  32. 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. https://doi.org/10.3831/KPI.2006.9.2.079
  33. 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. https://doi.org/10.3831/KPI.2006.9.3.061
  34. Renata MS, Jorge A, Hugo V. Structural and functional behavior of biologically active monomeric melittin. J Molecular Graphics and Modelling. 2007; 25: 767-772. https://doi.org/10.1016/j.jmgm.2006.06.006
  35. 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. https://doi.org/10.1067/msy.2001.116672
  36. Aranha MM. $NF-{\kappa}B$ and apotosis in colorectal tumorigenesis. Eur J Clin Invest. 2007; 37: 416-424. https://doi.org/10.1111/j.1365-2362.2007.01801.x

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