DOI QR코드

DOI QR Code

Study of a 13-weeks, Repeated, Intramuscular Dose, Toxicity Test of Sweet Bee Venom in Sprague-Dawley Rats

  • Kang, Hyunmin ;
  • Lim, Chungsan ;
  • Kwon, Ki-Rok ;
  • Lee, Kwangho
  • Received : 2013.11.07
  • Accepted : 2014.02.12
  • Published : 2014.06.30

Abstract

Objectives: This study was performed to analyze a 13-week repeated dose toxicity test of Sweet Bee Venom (SBV) extracted from bee venom and administered in Sprague-Dawley (SD) rats. Methods: Male and female 5-week-old SD rats were treated once daily with SBV (high-dosage group: 0.28 mg/kg; medium-dosage group: 0.14 mg/kg; or low-dosage group: 0.07 mg/kg) for 13 weeks. Normal saline was administered to the control group in a similar manner (0.2 mL/kg). We conducted clinical observations, body weight measurements, ophthalmic examinations, urinalyses, hematology and biochemistry tests, and histological observations using hematoxylin and eosin (H&E) staining to identify any abnormalities caused by the SBV treatment. Results: During this study, no mortality was observed in any of the experimental groups. Hyperemia and a movement disorder were observed around the area of in all groups that received SBV treatment, with a higher occurrence in rats treated with a higher dosage. Male rats receiving in the high-dosage group showed a significant decrease in weight during the treatment period. Compared to the control group, no significant changes in the ophthalmic parameters, the urine analyses, the complete blood cell count (CBC), and the biochemistry in the groups treated with SBV. Compared to the control group, some changes in organ weights were observed in the medium-and the high-dosage groups, but the low-dosage group showed no significant changes. Histological examination of thigh muscle indicated cell infiltration, inflammation, degeneration, and necrosis of muscle fiber, as well as fibrosis, in both the medium- and the high-dosage groups. Fatty liver change was observed in the periportal area of rats receiving medium and high dosages of SBV. No other organ abnormalities were observed. Conclusion: Our findings suggest that the No Observed Adverse Effect Level (NOAEL) of SBV is approximately 0.07 mg/kg in male and female SD rats.

Keywords

intramuscular;melittin;pharmacopuncture;rats;sweet bee venom;13 weeks repeated dose toxicity

References

  1. Kin KU, Seo BM, Yun JS, Lee YK, Choi SH, Lee KM, et al. [The comparison of bee venom herbal-acupuncture 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):181-7. Korean.
  2. 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]. J Pharmacopunct. 2006;9(2):105-12. Korean. https://doi.org/10.3831/KPI.2006.9.2.105
  3. Lee JS, Lee JY, Kwon KR, Lee HC. [A study on allergic response between bee venom and sweet bee venom pharmacopunture]. J Pharmacopunct. 2006;9(3):61-77. Korean. https://doi.org/10.3831/KPI.2006.9.3.061
  4. Korean Pharmacopuncture Institute. Pharmacopuncturology: principles and clinical applications. Seoul: Elsevier Korea LLC; 2012. Chapter 09, Animal Based Pharmacopuncture; p. 147-9.
  5. Lee SN, Hong SY, Jo HC, Byun IJ, Song HS, Kim KH. [The clinical study on bee venom acupuncture treatment on osteoarthritis of knee Joint]. The Journal of Korean Acupuncture & Moxibustion Society. 2003;20(5):73-81. Korean.
  6. 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. Korean.
  7. Kim TH. Kang KS, Kwon GR. [Three cases of affections of the hip treated with Korean Bee-Venom therapy]. J Pharmacopunct. 2001;4(3):127-34. Korean. https://doi.org/10.3831/KPI.2001.4.3.127
  8. Lee SH, Lee HJ, Baek YH, Kim SY, Park JK, Hong SJ, et al. [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. Korean.
  9. Lee SH, Hong SJ, Kim SY, Yang HI, Lee JD, Choi DY, et al. [Randomized Controlled Double Blind Study of Bee Venom Therapy on Rheumatoid Arthritis]. The Journal of Korean Acupuncture & Moxibustion Society. 2003;20(6):80-8. Korean.
  10. Kwon KR, Chu CS, Park HS, Kim MK, Cha BC, Lee E. [Experimental studies of quantitative evaluation using HPLC and safety of Sweet Bee Venom]. J Pharmacopunct. 2007;10(2):81-6. Korean. https://doi.org/10.3831/KPI.2007.10.2.081
  11. 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. Korean.
  12. Ko HK. [Experimental studies on the effect of bee venom therapy on the analgesic, anti-pyretic and anti-inflammatory action]. Korean Journal of Oriental Medicine. 1992;13(1):283-92. Korean.
  13. Kim YJ, Lim CS, Kwon KR. [Study of single dose test of Sweet Bee Venom in rats]. J Pharmacopunct.2009;12(4).5-32. Korean.
  14. Yoon HC, Lee KH, Kwon KR. [Study of single dose toxic test of sweet bee venom in beagle dogs]. J Pharmacopunct. 2010;13(4):43-62. Korean. https://doi.org/10.3831/KPI.2010.13.4.043
  15. Kwon HY, Kwon KR. [Study of four weeks repeated-dose toxic test of sweet bee venom in rats]. J Pharmacopunct. 2011;14(1):5-24. Korean. https://doi.org/10.3831/KPI.2011.14.1.005
  16. Park JS, Lee KH, Kwon KR. [Study of four week repeated dose toxic test of sweet bee venom in beagle dogs]. J Pharmacopunct. 2010;13(4):5-41. Korean. https://doi.org/10.3831/KPI.2010.13.4.005
  17. Bartlett MS. Properties of sufficiency and statistical test. Pros R Soc London A. 1937;160(901):268-82. https://doi.org/10.1098/rspa.1937.0109
  18. Dunnett CW. New tables for multiple comparisons with control. Biometrics. 1964;20(3):482-91. https://doi.org/10.2307/2528490
  19. Kwon KR, Choi SH, Cha BC. [Component analysis of sweet BV and clinical trial on antibody titer and allergic reactions]. J Pharmacopunct. 2006;9(2):79-86. Korean. https://doi.org/10.3831/KPI.2006.9.2.079
  20. Lee GM, Lee KS, Yeom SC, Jang JH, Yun JY, Hwang BC, et al. [A clinical study of bee-venom acupuncture treatment on protrusion disc Patients]. The Journal of Korean Acupuncture & Moxibustion Society. 2004;21(5):13-26. Korean.
  21. Habermann E. Bee and wasp venoms. Science. 1972;177(4046):314-22. https://doi.org/10.1126/science.177.4046.314
  22. Gauldie J, Hanson JM, Rumjanek FD, Shipolini RA, Vernon CA. The Peptide Components of Bee Venom. Eur. J. Biochem. 1976;61(2):369-76. https://doi.org/10.1111/j.1432-1033.1976.tb10030.x
  23. Lee JS, Lee JY, Kwon KR, Lee HC. [A Study on allergic response between bee venom and sweet bee venom pharmacopunture]. J Pharmacopunct. 2006;9(3):61-77. Korean. https://doi.org/10.3831/KPI.2006.9.3.061

Cited by

  1. Intravenous Single Dose Toxicity of Sweet Bee Venom in Sprague-Dawley Rats vol.18, pp.3, 2015, https://doi.org/10.3831/KPI.2015.18.024
  2. Toxicity of Single-dose Intramuscular Injection of Samjeong Pharmacopuncture in Sprague-Dawley Rats vol.18, pp.2, 2015, https://doi.org/10.3831/KPI.2015.18.016