Study of toxic effects of Submastin-KRS by multiple intramuscular injection in rats

DOI 10.33861/2071-8020-2021-3-7-10

Gritsyuk V.A., Vostroilova G.A., Chaplygina Yu.A., Khokhlova N.A.

Summary. Inflammation of the mammary gland of cows, which occurs against the background of adverse environmental factors, currently remains an urgent problem and is the cause of significant economic losses at livestock complexes. Currently, one of the options for anti-mastitis therapy without the use of antibiotics is the use of immunostimulating drugs based on recombinant interferons, which have a wide spectrum of action due to the activation of the immune system. Submastin-KRS is a composition of recombinant species-specific cytokines for cattle, with a total activity of at least 104 IU and vitamin A (75000 IU), contained in 1 ml of the drug. The study of the general toxicity of drugs is carried out in order to study the preclinical properties of the drug and for further risk assessment during clinical trials. The objective of the work was to determine the parameters of the toxicity of the drug Submastin-KRS in a subacute experiment. Healthy adult white outbred rats of both sexes were used as test systems. Submastin-KRS was administered for 30 days once a day at doses of 0.1 and 1.0 ml/kg (therapeutic dose and 10 times higher one). The general toxic effect of the drug was assessed daily by appearance, general state, behavior, weekly - by the dynamics of body weight, at the end of the course of the drug Submastin-KRS - by hematological indicators and the state of the hemostasis system. A preclinical study of the subacute toxicity of Submastin-KRS with its repeated administration to rats at doses of 0.1 and 1.0 ml/kg showed the absence of general toxic effects. There were no deviations in behavior, food and water consumption, body weight and temperature dynamics. The study drug did not cause changes in the relative mass of internal organs and their morphological structure. Repeated use of Submastin-KRS did not lead to the appearance of significant changes in the blood of the animals of the experimental groups from the side of morphological and biochemical indicators. The study did not detect any data that prevent the clinical trial of the drug Submastin-KRS.

Keywords: large horned cattle, mastitis, Submastin-KRS, recombinant cytokines, preclinical studies, subacute toxicity, white rats, general toxic effect, target organs, morphology, blood biochemistry, pathomorphology.

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Author affiliation:

Gritsyuk Vasilina A., Ph.D. in Agriculture, doctoral student, leading scientific researcher of the Department of Experimental Pharmacology of the AllRussian Veterinary Research Institute of Pathology, Pharmacology and Therapy; 114 b, Lomonosova st., Voronezh, 394087; phone: 8-903-6526316; e-mail: vnivipat@mail.ru.

Vostroilova Galina A., D.Sc. in Biology, chief scientific researcher of the Department of Experimental Pharmacology of the All-Russian Veterinary Research Institute of Pathology, Pharmacology and Therapy; 114 b, Lomonosova st., Voronezh, 394087; phone: 8-906-6781203; e-mail: gvostroilova@mail.ru.

Chaplygina Yuliya A., junior scientific researcher of the Department of Experimental Pharmacology of the All-Russian Veterinary Research Institute of Pathology, Pharmacology and Therapy; 114 b, Lomonosova st., Voronezh, 394087; phone: 8-951-5553510; e-mail: kantorovich.yuliya@mail.ru.

Responsible for correspondence with the editorial board: Khokhlova Nina A., scientific researcher of the Department of Experimental Pharmacology of the All-Russian Veterinary Research Institute of Pathology, Pharmacology and Therapy; 114 b, Lomonosova st., Voronezh, 394087; phone: 8-908-1376923; e-mail: nina_xoxlova@mail.ru.