DOI QR코드

DOI QR Code

Acute Toxicity of Crude Anti-fungal Compounds Produced by Lactobacillus plantarum AF1

Lactobacillus plantarum AF1이 생성한 조항진균 물질의 마우스에 대한 급성독성

  • Received : 2013.01.29
  • Accepted : 2013.03.21
  • Published : 2013.06.30

Abstract

We investigated the acute toxicity from a single dose of crude anti-fungal compounds produced by Lactobacillus plantarum AF1, a lactic acid bacterium isolated from kimchi, on ICR male and female mice in vivo. The test article was orally administered once to both sexes of mice. The mortality rate, clinical findings, autopsy findings, and body weight changes were monitored daily for 14 days. In the oral acute toxicity test, male and female mice were gavaged with four doses (5, 50, 300 or 2,000 mg/kg) of the crude anti-fungal compounds. The oral $LD_{50}$ of the crude anti-fungal compounds was higher than 2,000 mg/kg. No significant changes in general conditions, body weights, clinical signs, or appearance of gross lesions were observed. In conclusion, our results suggest a low toxicity and no-adverse-effects from crude anti-fungal compounds produced by Lactobacillus plantarum AF1 up to 2,000 mg/kg via the oral route.

본 연구는 김치로부터 항진균 활성을 보이는 유산균인 Lactobacillus(Lb.) plantarum AF1이 생산하는 조항진균 물질의 부분 정제물이 천연 식품보존제 및 사료보존제로서 사용 가능성을 알아보기 위하여 안전성을 평가하고자 단회 급성독성시험을 실시하였다. 급성독성시험을 위하여 경구로 1회 시험물질을 최고 용량(2,000 mg/kg)으로 하여 ICR계통 암수 마우스에게 용량별 각 군당 10 마리씩 투여한 후 14일간의 일반증상, 사망률, 체중, 임상증상 및 육안적 소견을 관찰하였다. 단회 경구투여한 후 모든 시험군에서 사망례가 관찰되지 않았으며, 시험동물은 시험 종료 시까지 계속 생존하여 평균치사량을 산출할 수 없었다. 경구투여한 후 마우스의 체중변화에 있어서도 암수 모두 대조군과 시료물질 투여군 사이에 유의성 있는 차이는 보이지 않았으며, 용량 의존적인 차이도 볼 수 없었다. 경구투여한 후 시험 종료한 다음 생존동물 모두를 부검하여 주요 장기의 육안적 소견을 관찰한 결과 대조군과 시료투여군 모두에서 외관상이나 내부 장기에 어떠한 이상소견이나 병변이 관찰되지 않았다. 이상의 결과로부터 시험물질인 Lb. plantarum AF1이 생산한 조항진균 물질을 경구투여 시 ICR계통 암수 마우스에서 독성학적인 변화가 관찰되지 않았으며, $LD_{50}$은 경구투여 시 2,000 mg/kg 이상인 저독성의 안전한 물질로 사료된다.

Keywords

References

  1. Galvano F, Piva A, Ritieni A, Galvano G. 2001. Dietary strategies to counteract the effects of mycotoxins: a review. J Food Prot 64: 120-131. https://doi.org/10.4315/0362-028X-64.1.120
  2. Brul S, Coote P. 1999. Preservative agents in foods. Mode of action and microbial resistance mechanisms. Int J Food Microbiol 50: 1-17. https://doi.org/10.1016/S0168-1605(99)00072-0
  3. Davidson MP. 2001. Chemical preservatives and natural antimicrobial compounds. In Food Microbiology: Fundamentals and Frontiers. Doyle MP, Beuchat LR, Montville TJ, eds. ASM press, Washington, DC, USA. p 593-627.
  4. Sanglard D. 2002. Resistance of human fungal pathogens to antifungal drugs. Curr Opin Microbiol 5: 379-385. https://doi.org/10.1016/S1369-5274(02)00344-2
  5. Yang EJ, Chang HC. 2008. Antifungal activity of Lactobacillus plantarum isolated from kimchi. Kor J Microbiol Biotechnol 36: 276-284.
  6. Yang EJ, Chang HC. 2010. Purification of a new antifungal compound produced by Lactobacillus plantarum AF1 isolated from kimchi. Int J Food Microbiol 139: 56-63. https://doi.org/10.1016/j.ijfoodmicro.2010.02.012
  7. Earnshaw RG. 1992. The antimicrobial action of lactic acid bacteria: Natural food preservation systems. In The Lactic Acid Bacteria in Health And Disease . Wood BJB, ed. Elsevier, London, UK. p 211-232.
  8. Bang JH, Shin HJ, Choi HJ, Kim DW, Ahn CS, Jeong YK, Joo WH. 2012. Probiotic potential of Lactobacillus isolates. J Life Sci 22: 251-258. https://doi.org/10.5352/JLS.2012.22.2.251
  9. Ahn JE, Kim JK, Lee HR, Eom HJ, Han NS. 2012. Isolation and characteristics of a bacteriocin-producing Lactobacillus sakei B16 from Kimchi. J Korean Soc Food Sci Nutr 41:721-726. https://doi.org/10.3746/jkfn.2012.41.5.721
  10. Kim GE. 2011. Characteristics & applications of Lactobacillus sp. from Kimchi. Korean Soc Biotechnol Bioengine J 26:374-380.
  11. Shida K, Makino K, Morishita A, Takamizawa K, Hachimura S, Ametani A, Sato T, Kumagai Y, Habu S, Kaminogawa S. 1998. Lactobacillus casei inhibits antigen-induced IgE secretion through regulation of cytokine production in murine splenocyte cultures. Int Arch Allergy Immnunol 115:278-287. https://doi.org/10.1159/000069458
  12. Resta-Lenert S, Barett KE. 2006. Probiotics and commensals reverse TNF-${\alpha}$- and IFN-${\gamma}$-induced dysfunction in human intestinal epithelial cells. Gastroenterology 130:731-746. https://doi.org/10.1053/j.gastro.2005.12.015
  13. Klaenhammer TR. 1988. Bacteriocins of lactic acid bacteria. Biochimie 70: 337-349. https://doi.org/10.1016/0300-9084(88)90206-4
  14. Stiles ME 1996. Biopreservation by lactic acid bacteria. Antonie Van Leeuwenhoek 70: 331-345. https://doi.org/10.1007/BF00395940
  15. Messens W, De VL. 2002. Inhibitory substances produced by Lactobacilli isolated from sourdoughs-a review. Int J Food Microbiol 72: 31-43. https://doi.org/10.1016/S0168-1605(01)00611-0
  16. Atrih A, Rekhif N, Milliere JP, Lefebvre G. 1993. Detection and characterization of a bacteriocin produced by Lactobacillus plantarum C19. Canadian J Microbiology 39: 1173-1179. https://doi.org/10.1139/m93-178
  17. Klaver FA, van der Meer R. 1993. The assumed assimilation of cholesterol by Lactobacilli and Bifidobacterium bifidum is due to their bile salt-deconjugating activity. Appl Environ Microbiol 59: 1120-1124.
  18. Alander M, Satokari R, Korpela R, Saxelin M, Vilpponen-Salmela T, Mattila-Sandholm T, von Wright A. 1999. Persistence of colonization of human colonic mucosa by a probiotic strain, Lactobacillus rhamnosus GG, after oral consumption. Appl Environ Microbiol 65: 351-354.
  19. Seo J, Lee GS, Kim JE, Chung MJ. 2010. Development of probiotic products and challengers. KSBB J 25: 303-310.
  20. Tagg JR, Dajani AS, Wannamaker LW. 1976. Bacteriocins of gram-positive bacteria. Bacteriol Rev 40: 722-756.
  21. Drider D, Fimland G, Hechard Y, McMullen LM, Prevost H. 2006. The continuing story of class IIa bacteriocins. Microbiol Mol Biol Rev 70: 564-582. https://doi.org/10.1128/MMBR.00016-05
  22. Lee SG, Han KS, Jeong SG, Oh MH, Jang AR, Kim DH, Bae IH, Ham JS. 2010. A study on the sensory characteristic of yogurt and antimicrobial activity of Lactobacillus plantarum LHC52 isolated form Kimchi. Korean J Food Sci Ani Resour 30: 328-335. https://doi.org/10.5851/kosfa.2010.30.2.328
  23. Lee H, Lee JJ, Chang HC, Lee MY. 2012. Acute toxicity of Lactobacillus plantarum AF1 isolated from kimchi in mice. Korean J Food Preserv 19: 315-321. https://doi.org/10.11002/kjfp.2012.19.2.315
  24. Lee JJ, Kim AR, Chang HC, Lee MY. 2011. Repeated-dose oral toxicity study of Lactobacillus plantarum AF1 isolated from kimchi in rats. J Korean Soc Food Sci Nutr 41:612-620. https://doi.org/10.3746/jkfn.2012.41.5.612
  25. Yang EJ. 2008. Application of kimchi lactic acid bacteria and Bacillus subtilis for development of novel antibiotics and edible vaccine. PhD Dissertation. Chosun University, Gwangju, Korea.
  26. Guidelines for toxicity tests of drugs and related materials notification. 2009. KFDA. Korea. p 1-5.
  27. Good laboratory practice regulation for non-clinical laboratory studies. 2009. KFDA. Korea. p 1-74.
  28. Organization for economic cooperation and development (OECD). 2001. OECD guideline for the testing of chemicals revised draft guideline 420.
  29. Cho YR, Yun YN, Han ES, Kwak SJ, Kim HS, Kang MS, Lee JY, Oh JH, Lim CH, Kim DS, Kim SH, Kang TS. 2008. Internal establishment and validation of OECD guidelines of acute oral toxicity. J Alternative Animal Experiments 2: 21-33.
  30. Donohue DC, Deighton M, Ahokas JT, Salminen S. 1993. Toxicity of lactic acid bacteria. In Lactic Acid Bacteria. Salminen S, von Wright A, eds. Marcel Dekker, New York, NY, USA. p 307-313.
  31. OECD/OECD 420. 2001. Oecd guideline for testing of chemicals: Acute oral Toxicity-Fixed Dose Procedure.
  32. Sass N. 2000. Humane endpoints and acute toxicity testing. ILAR J 41: 114-123. https://doi.org/10.1093/ilar.41.2.114
  33. Schled E, Genschow E, Spielmann H, Stropp G, Kayser D. 2005. Oral acute toxic class method: a successful alternative to the oral LD50 test. Regul Toxicol Pharmacol 42: 15-23. https://doi.org/10.1016/j.yrtph.2004.12.006
  34. Toth LA. 2000. Defining the moribund condition as an experimental endpoint for animal research. ILAR J 41: 72-79. https://doi.org/10.1093/ilar.41.2.72
  35. Korean Food Standards CODEX. 2012. Korean Food and Drug Administration.
  36. Donohue DC, Salminen S. 1996. Safety of probiotic bacteria. Asia Pacific J Clin Nutr 5: 25-28.
  37. Ozlem O, Fadime K, Ingolf FN. 2011. A probiotic bacterium, Pediococcus pentasaceus OZF, isolated from human breat milk products AcH/PA-1. Afr J Food Sci 10: 2070-2079.

Cited by

  1. Identification of Antifungal Substances of Lactobacillus sakei subsp. ALI033 and Antifungal Activity against Penicillium brevicompactum Strain FI02 vol.21, pp.1, 2016, https://doi.org/10.3746/pnf.2016.21.1.52
  2. Acute and Subacute Oral Toxicity Evaluation of Crude Antifungal Compounds Produced by Lactobacillus plantarum HD1 in Rats vol.20, pp.3, 2015, https://doi.org/10.3746/pnf.2015.20.3.190
  3. Oral Toxicity of Crude Antifungal Compounds Produced by Lactobacillus Plantarum AF1 and Lactobacillus Plantarum HD1 vol.26, pp.3, 2015, https://doi.org/10.7856/kjcls.2015.26.3.511