Toxicity assessment of the drug based on silver nanoparticles and proteolytic enzyme

One of the most relevant areas of veterinary science is the search for new, environmentally safe, antimicrobial drugs. From this position, special attention should be paid to products based on ionized silver. As part of preclinical studies, the toxic properties of a new complex drug containing nanoserebro and a proteolytic enzyme as active substances were determined. The toxicity study was performed on healthy sexually Mature out-bred white male mice with a live weight of 20-24 grams. The effect of a single dose was determined by intragastric (n=7) and intra-peritoneal administration (n=7), chronic toxicity was determined by introperitoneal administration of the drug for 14 days (n=12). A control group of mice was given saline. The toxic effects of the drug were assessed by changes in behavioral response, appetite, body weight, and the number of fatalities. At the end of the experiment, the surviving mice were euthanized, the hematological properties of the blood and the state of internal organs were evaluated. In the course of studies, it was not possible to establish a lethal dose of the drug, since the maximum allowable volume for intragastric and intra-peritoneal administration (1.0 ml) did not cause it. The tolerated dose of this drug with single and multiple administration was more than 40,000 mg/kg of body weight, which in accordance with GOST 12.1.007-76 allows it to be classified as class 4 toxicity (more than 5,000 mg/kg when administered in the stomach). The use of the drug for two weeks caused minor reversible morphological changes in the blood in mice: hyperchromia (an increase in hemoglobin by 2.3 PG / ml; P<0.05) and more pronounced anisocytosis of red blood cells (by 2.7%; P<0.001), without any macroscopic changes in internal organs. Thus, the results obtained reflect the weak toxic effect of the drug, which allows us to go directly to its clinical trials.

доклинические исследования, наносеребро, протеолитические ферменты, острая и хроническая токсичность, preclinical studies, nanosilver, a proteolytic enzyme, acute and chronic toxicity

1. Бледных Л.В. Антимикробные и токсикологические свойства озонированного льняного масла/ Л.В.Бледных, С.В. Николаев, И.Г. Конопельцев //Ветеринарный врач, 2017.- №3. - С.44-51.

2. Буиклиский В.Д., Сирота А.В., Зайцев A.С., Беспалов А.В., Письменская Н.Д., Систа Ф., Коба И.С. Формирование биологически активной композиции наночастиц серебра, стабилизированных сополимером акриловой кислоты и акриламида // Нанотехника. - 2008. -№13. - С. 88-93.

3. Муха Ю.П., Еременко А.М., Смирнова Н.П., Михиенкова А.И., Корчак Г.И., Горчев B.Ф., Чунихин А.Ю. Антимикробная активность стабильных наночастиц серебра заданного размера//Прикладная биохимия и микробиология. -2013. -Т. 49, № 2. -С. 215.

4. Николаев С.В. Эффективность озонированной эмульсии при профилактике послеродового эндометрита у коров и ее влияние на эндометрий/ С.В. Николаев, И.Г. Конопельцев // Вопросы нормативно - правового регулирования в ветеринарии. - 2019. - № 1. - С. 69 - 74.

5. Новикова Е.Н. Применение нового средства для лечения эндометрита бактериальной и микозной этиологии / Е.Н. Новикова, М.Б. Решетка, И.С. Коба, М.С. Дубовикова // Вопросы нормативно-правового регулирования в ветеринарии. 2014. № 3. С. 138-140.

6. Филатов А.В. Антимикробные средства озонированных растворов/А.В.Филатов, И.Г.Конопельцев, Е.В.Черных // Нижегородский медицинский журнал. Озонотерапия. -2003.

7. Хабриев, Р.У. Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ / Р.У. Хабриев. -М.: Медицина, 2005. - 832 с.

8. Bademkiran, S. Comparison of Pelargoni-umsidoides, Placebo and Antibiotic Treatment of Chronic Endometritis in Dairy Cows: A Field Trial/S. Bademkiran,D. Kurt JB. Yokusand, R. Celik//Journal of Animal and Veterinary Advances-2009, Volume: 8, Issue: 4, Pages 788-793.

9. Cheong S.H., Nydam D.V., Galvao K.N., Crosier B.M., Gilbert R.O. Cow and herd-level risk factors for subclinical endometritis in lactating Holstein cows. J. Dairy Sci. 2011, Pages 762-770. DOI: 10.3168/jds.2010-3439