title: Safety of lysosubtilin per os in mice, rabbits and calves.
abstract: Lysosubtilin is a broad-spectrum preparation of lytic enzymes from Bacillus subtilis designed for veterinary medicine as an alternative to common antibiotics. The safety of lysosubtilin was studied in acute and subchronic toxicity tests in mice, rabbits, and calves. No sign of toxicosis was observed when lysosubtilin was administered as a single dose per os to white mice in doses reaching 2 x 10(6) U/kg of weight. Subcutaneous LD50 of lysosubtilin in mice was equal to 5 x 10(5) U/kg of weight. In order to determine subchronic toxicity in mice and rabbits the doses of lysosubtilin used in veterinary practice (2 x 10(4) U/kg of weight) were increased up to ten times (2, 8, 20.10(4) U/kg of weight) and when experimenting with calves they were increased up to two times (4.10(4) U/kg of weight) while extending the administration period by three times. In the three animal species, given in increased doses twice a day per os for 30 days, lysosubtilin did not cause any evident signs of clinical toxicosis. The blood and sera indices of rabbits and calves were within the normal range. In calves the changes were insignificant. The ANOVA test, however, revealed statistically significant differences in hemoglobin, WBC, protein, and glucose value changes between rabbit groups which were given different doses of lysosubtilin. A significant increase in daily weight gain (approximately 100 g, P < 0.001), influenced by lysosubtilin, was observed in calves. No deviations from the normal status were observed in the organs and tissues obtained during the post-mortem examination of rabbits and calves slaughtered 1 and 15 days after the end of lysosubtilin administration. Veterinary-sanitary examination of the slaughtered animals and laboratory tests of their meat showed normal commercial and sanitary qualities.
authors.affiliation: Institute of Immunology, Sector of Immunobiotechnology, Vilnius, Lithuania.
authors.forename: G A
authors.initials: GA
authors.lastname: Biziulevichius
authors.forename: I G
authors.initials: IG
authors.lastname: Arestov
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D001412:Bacillus subtilis; D001772:Blood Cell Count / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D051379:Mice; D008815:Mice, Inbred Strains; D011817:Rabbits; D013381:Subtilisins / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; C061754:lysosubtilin G10X; D013381:Subtilisins