This experiment was conducted to evaluate the acute toxicity of the bacteriocin Subticin 112 secreted by Bacillus subtilis, and to determine the medium lethal dose (LD50) or maximum tolerated dose (MTD) in mice after oral administration. Eighty SPF KM mice with body weight of (20±2) g were randomly divided into four groups with the ratio of male∶female as 1∶1 for each group. Mice in the control group were given 0.4 mL of sterile saline, and mice in the other three experimental groups were given 0.4 mL 0.25, 0.50 and 1.00 g/mL subticin 112 solution, respectively. After oral administration, the symptoms and mortality were observed and recorded carefully for 14 days. After the experiment, we recorded the weight gain, and then blood samples were collected from the eye vein by quickly removing the eyeball to determine the biochemical indices in serum. After dissecting all the mice, the heart, liver, spleen and kidney were weighed accurately to determine the organ coefficient, and 2 organ samples of each group were picked for histopathology examination. After oral administration for 14 days, the mice in each group were alive and did not show any abnormal symptoms. The weight gain of mice in experimental groups had a decreasing trend (P>0.05). Organ coefficients and biochemical indices in serum of mice in each group were not significantly different (P>0.05). And according to the results of histopathology examination, no pathological changes were observed. Through the experiment, we conclude that the maximum tolerated dose (MTD) of the bacteriocin Subticin 112 is higher than 20 g/kg BW. According to the national standard of acute toxicity test (GB 15193.3—2003), Subticin 112 belongs to a non-toxic medicine. ［Chinese Journal of Animal Nutrition, 2011, 23（8）：1446 -1452］
DENG Kai,ZHANG Rijun
. Acute Toxicity of Bacteriocin Subticin 112 in Mice[J]. Chinese Journal of Animal Nutrition, 2011
, 23(08)
: 1446
-1452
.
DOI: 10.3969/j.issn.1006-267x.2011.08.026
［1］NES I F, DIEP D B, HOLO H. Bacteriocin diversity in Streptococcus and Enterococcus[J]. Journal of Bacteriology, 2007, 189(4):1189-1198.
[2]BABA T, SCHNEEWIND O. Instruments of microbial warfare: bacteriocin synthesis, toxicity and immunity[J]. Trends in Microbiology, 1998, 6(2):66-71.
[3]ABEE T, KROCKEL L, HILL C. Bacteriocins: modes of action and potentials in food preservation and control of food poisoning[J]. International Journal of Food Microbiology, 1995, 28(2):169-185.
[4]CLEVELAND J, MONTVILLE T J, NES I F, et al. Bacteriocins: safe, natural antimicrobials for food preservation[J]. International Journal of Food Microbiology, 2001, 71(1):1-20.
[5]ENNAHAR S, SASHIHARA T, SONOMOTO K, et al. Class IIa bacteriocins: biosynthesis, structure and activity[J]. Microbiology Reviews, 2000, 24(1):85-106.
[6]RASHID M H, TOGO K, UEDA M, et al. Characterization of bacteriocin produced by Streptococcus bovis J2 40-2 isolated from traditional fermented milk ‘Dahi’[J]. Animal Science Journal, 2009, 80(1): 70-78.
[7]XIE J H, ZHANG R J, SHANG C J, et al. Isolation and characterization of a bacteriocin produced by an isolated Bacillus subtilis LFB112 that exhibits antimicrobial activity against domestic animal[J]. African Journal of Biotechnology, 2009, 8(20):5611-5619.
[8]SOSA S, FAVERO G D, BORTOLI M D, et al. Palytoxin toxicity after acute oral administration in mice[J]. Toxicology Letters, 2009, 191(2/3):253-259.
[9]DANIELE D, FERREIRA S, ESPERANDIM V R, et al. Trypanocidal activity and acute toxicity assessment of triterpene acids[J]. Parasitology Research, 2010, 106(4): 985-989.
[10]AMIT K M, NAVEEN A, SHAILENDRA N G, et al. Acute toxicity assessment of choline by inhalation, intraperitoneal and oral routes in Balb/c mice[J]. Regulatory Toxicology and Pharmacology, 2009, 54(3):282-286.
[11]WANG J X, ZHOU G Q. Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration[J]. Toxicology Letters, 2007, 168(2):176-185.
[12]MANUEL A, PABLO D, JOSEE J, et al. Evaluation of immunomodulatory effects of nisin-containing diets on mice[J]. Immunology and Medical Microbiology, 1999, 24(1):35-42.
[13]SADHANA M, CLARA C, ARANHA K, et al. Evaluation of developmental toxicity of microbicide Nisin in rats[J]. Food and Chemical Toxicology, 2008, 46(2):598-603.
[14]ARANHA C, SADHANA G, REDDY K. Contraceptive efficacy of antimicrobial peptide Nisin: in vitro and in vivo studies[J]. Contraception, 2004, 69(4):333-338.
[15]REDDY K V R, ARANHA C, GUPTA S M, et al. Evaluation of antimicrobial peptide nisin as a safe vaginal contraceptive agent in rabbits: in vitro and in vivo studies[J]. Reproduction, 2004, 128(1):117-126.
[16]INGHAM A, FORD M, MOORE R J, et al. The bacteriocin piscicolin 126 retains antilisterial activity in vivo[J]. Journal of Antimicrobial Chemotherapy, 2003, 51(6):1365-1371.
