Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

Subchronic Oral Dose Toxicity Study of Enterococcus Faecalis 2001 (EF 2001) in Mice

  • Gu, Yeun-Hwa (Department of Radiological Science, Faculty of Health Science, Junshin Gakuen University) ;
  • Yamasita, Takenori (Department of Radiological Science, Faculty of Health Science, Suzuka University of Medical Science) ;
  • Kang, Ki-Mun (Department of Oncology, Gyeongsang National University Hospital, Gyeongsang Institute of Health Sciences)
  • Received : 2017.05.18
  • Accepted : 2017.10.20
  • Published : 2018.01.15
Download PDF
⟨ Previous Next ⟩

Abstract

As a part of general toxicity studies of Enterococcus Faecalis 2001 (EF 2001) prepared using heat-treatment bacillus mort body EF 2001 in mice, this study examined the toxicity of EF 2001 in single and repeated administrations following the previous report in order to apply this product to preventive medicine. The safety of oral ingestion of EF 2001 was examined in 6-week-old male and female ICR mice with 1,000 mg/kg, 3,000 mg/kg and 5,000 mg/kg body weight/day administrated by gavage of the maximum acceptable dose of EF 2001. The study was conducted using distilled water as a control following the methods for general toxicity studies described in the "Guidelines for Non-clinical Studies of Pharmaceutical Products 2002". As a control, 1) observation of general conditions, 2) measurement of body weight, 3) determination of food consumption, 4) determination of water consumption, 5) blood test and urinalysis and 6) pathological examination were performed for the administration of EF 2001. Mice received EF 2001 for 13 weeks and results were compared with those of the control group that received distilled water. The results of the above examinations revealed no significant differences between control and EF 2001 groups for both males and females. Thus, no notable toxicity was confirmed with single and repeated oral administrations of EF 2001. Oral administration in the above doses did not result in abnormal symptoms or death during the observation period. No abnormalities in blood cell count or organ weights were seen. Without any evidence of toxicity to cells and organs, EF 2001 is speculated to not adversely affect living organisms. The 50% lethal dose of EF 2001 with oral administration in mice is estimated to be greater than 5,000 mg/kg body weight/day for both male and female mice. Therefore, $LD_{50}$ value for animals was 5,000 mg/kg or more.

Keywords

References

  1. Gupta, R., Sarkar, S. and Srivastava, S. (2014) In vivo toxicity assessment of antimicrobial peptides (AMPs LR14) Derived from Lactobacillus plantarum strain LR/14 in drosophila melanogaster. Probiotics Antimicrob. Proteins., 6, 59-67. https://doi.org/10.1007/s12602-013-9154-y
  2. Han, S.R., Yun, E.Y., Kim, J.Y., Hwang, J.S., Jeong, E. J. and Moon, K.S. (2016) Erratum to "evaluation of genotoxicity and 28-day oral dose toxicity on freeze-dried powder of tenebrio molitor larvae (yellow mealworm)". Toxicol. Res., 30, 121-130.
  3. Romano, A., Ladero, V., Alvarez, M.A. and Lucas, P.M. (2014) Putrescine production via the ornithine decarboxylation pathway improves the acid stress survival of Lactobacillus brevis and is part of a horizontally transferred acid resistance locus. Int. J. Food Microbiol., 175, 14-19. https://doi.org/10.1016/j.ijfoodmicro.2014.01.009
  4. Lee, S.M., Kim, H.J., Kim, S.Y., Kwon, M.K., Kim, S., Cho, A., Yun, M., Shin, J.S. and Yoo, K.H. (2014) Drug-loaded gold plasmonic nanoparticles for treatment of multidrug resistance in cancer. Biomaterials, 35, 2272-2282. https://doi.org/10.1016/j.biomaterials.2013.11.068
  5. Starke, I.C., Pieper, R., Neumann, K., Zentek, J. and Vahjen, W. (2014) The impact of high dietary zinc oxide on the development of the intestinal microbiota in weaned piglets. FEMS Microbiol. Ecol., 87, 416-427. https://doi.org/10.1111/1574-6941.12233
  6. Lopez-Rituerto, E., Avenoza, A., Busto, J.H. and Peregrina, J.M. (2013) NMR study of histidine metabolism during alcoholic and malolactic fermentations of wine and their influence on histamine production. J. Agric. Food Chem., 61, 9464-9469.
  7. Maggi, M., Negri, P., Plischuk, S., Szawarski, N., De Piano, F., De Feudis, L., Eguaras, M. and Audisio, C. (2013) Effects of the organic acids produced by a lactic acid bacterium in Apis mellifera colony development, Nosema ceranae control and fumagillin efficiency. Vet. Microbiol., 27, 474-483.
  8. Nakamura, T., Itokawa, Y., Tajima, M., Ukawa, Y., Cho, K.H., Choi, J.S., Ishida, T. and Gu, Y.H. (2007) Radioprotective effect of Lyophyllum decastes and the effect on immunological functions in irradiated mice. J. Tradi. Chi. Med., 27, 70-75.
  9. Patchen, M.L. and MacVittie, T.J. (1986) Comparative effects of soluble and particulate glucans on survival in irradiated mice. J. Biol. Response Mod., 5, 45-60.
  10. Gu, Y.H., Iwasa, M., Kobayashi, K., Cho, J.H., Yoo, B.G. and Kang, K.M. (2013) Radioprotective and antitumor effects of enterococcus faecalis in mice. J. Int. W.K. Cul., 1, 77-86.
  11. Park, J.M., Chang, K.H., Park, K.H., Choi, S.J., Lee, K.H., Lee, J.Y., Satoh, M., Song, S.Y. and Lee, M.Y. (2016) Differential effects between cigarette total particulate matter and cigarette smoke extract on blood and blood vessel. Toxicol. Res., 32, 353-358. https://doi.org/10.5487/TR.2016.32.4.353
  12. Okuno, T., Kashige, N., Satho, T., Irie, K., Hiramatsu, Y., Sharmin, T., Fukumitsu, Y., Uyeda, S., Yamada, S., Harakuni, T., Miyata, T., Arakawa, T., Imoto, M., Toda, A., Nakashima, Y. and Miake, F. (2013) Expression and secretion of cholera toxin B subunit in lactobacilli. Biol. Pharm. Bull., 36, 952-958. https://doi.org/10.1248/bpb.b12-01021
  13. Imbuluzqueta, E., Gamazo, C., Lana, H., Campanero, M.A., Salas, D., Gil, A.G., Elizondo, E., Ventosa, N., Veciana, J. and Blanco-Prieto, M.J. (2013) Hydrophobic gentamicin-loaded nanoparticles are effective against Brucella melitensis infection in mice. Antimicrob. Agents Chemother., 57, 3326-3333. https://doi.org/10.1128/AAC.00378-13
  14. Candelario, K.M., Shuttleworth, C.W. and Cunningham, L.A. (2013) Neural stem/progenitor cells display a low requirement for oxidative metabolism independent of hypoxia inducible factor-1alpha expression. J. Neurochem., 25, 420-429.
  15. Zhang, K., Cheng, L., Imazato, S., Antonucci, J.M., Lin, N.J., Lin-Gibson, S., Bai, Y. and Xu, H.H. (2013) Effects of dual antibacterial agents MDPB and nano-silver in primer on microcosm biofilm, cytotoxicity and dentine bond properties. J. Dent., 41, 464-474. https://doi.org/10.1016/j.jdent.2013.02.001
  16. Uniform Requirements for Manuscripts Submitted to Biomedical Journals, International Committee of Medical Journal Editors (ICMJE).
  17. Hanaoka, H., Naito, S., Toyoda, Y., Matsukawa, H., Suzuki, N., Hirata, H., Nozu, K., Oda, S. and Eda, Y. (2004) Repeated mixed feeding toxicity test using lactic acid bacteria (Lactobacillus salivarius WB21 strain) for 13 weeks. Applied Pharmacology, 66, 4-36.
  18. Saito, K. (1989) 3-month oral subchronic (90-day) toxicity experiment of beraprost sodium in rats. Fundamentals and Clinical Pharmacology, 23, 3412.
  19. Yuki, N., Watanabe, K., Mike, A., Tagami, Y., Tanaka, R., Ohwaki, M. and Morotomi, M. (1999) Survival of a probiotic, EF2001 casei strain Shirota, in the gastrointestinal tract: selective isolation from faeces and identification using monoclonal antibodies. Int. J. Food Microbiol., 48, 51-57.
  20. Kim, K.W. (2015) Effects of styrene-metabolizing enzyme polymorphisms and lifestyle behaviors on blood styrene and urinary metabolite levels in workers chronically exposed to styrene. Toxicol. Res., 31, 355-361. https://doi.org/10.5487/TR.2015.31.4.355