Advanced research for physico-chemical properties and parameters of toxicity piperazinium 2-((5-(furan-2-YL)-4-phenyl-4H-1,2,4-triazol-3-YL)THIO)acetate

Karpenko, Yu. V.; Hunchak, Yuliia; Gutyj, Bohdan; Hunchak, Alla; Parchenko, Maryna; Парченко, В. В.

doi:10.15587/2519-4852.2022.255848

Cited by 31 publications

(33 citation statements)

References 9 publications

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“…Залежно від кількості введеного препарату "Авізуріл" визначали середньосмертельну дозу (DL 50 ) та визначали показники гострої токсичності з використанням методів Г. Кербера (1931) та Г. Першина (1939, 1950) (Karpenko et al, 2022;Varkholiak et al, 2022).…”

Section: матеріал і методи дослідженьunclassified

Determination of acute toxicity of antiprotozoal drug “Avizuril”

Hunko

Фотіна

2022

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Chickenpox is an intestinal disease that disrupts growth and suppresses the immune system, leading to high mortality, which researchers estimate is more than $ 3 billion annually in poultry. However, a significant problem of modern animal husbandry and especially poultry farming is the emergence of resistance in Eimeria to almost all coccidiostats. It is possible to prevent and prevent the emergence of drug resistance only by rotating the drugs with different active substances. For this purpose, 3–4 different drugs are used in the cultivation of animals and poultry. The goal of the work. In connection with the above purpose of the study was to determine the toxicity of the new antiprotozoal drug “Avizuril”. Depending on the amount of Avizuril administered, the mean lethal dose (DL50) and the main parameters of acute toxicity were determined using the methods of G. Kerber (1931) and G. Pershin (1939, 1950). To determine the toxicity of the drug used male and female white rats aged three months, weighing 180 ± 9.0 g. For feeding animals used feed according to a unified diet. Toxic effect of the drug “Avizuril” on experimental rats is observed at a dose of 1200 mg/kg. Based on the data on the calculation of the average lethal dose of the drug “Avizuril” when administered into the stomach by G. Kerber (1931), it was found that the DL50 for white rats is 1570 mg per 1 kg of animal weight. At autopsy, rats that died from acute poisoning were noted hyperemia and edema of the mucous membrane of the stomach and intestines, congestion in the lungs, heart and liver, enlargement of the spleen. At the next stage of research, the subtoxic dose of Avizuril was determined. Observations of animals showed that 1–3 hours after oral administration of the drug in a subtoxic dose in laboratory animals showed suffocation and depression of the central nervous system. Most of them died during the first day. Subsequent observations of the surviving animals showed that their motor response was suppressed for the next 24–72 hours. In studies of acute toxicity of the drug “Avizuril” it was found that when administered intragastrically to white rats DL50 for white rats is 1570 mg per 1 kg of animal weight. Studies of the effect of the subtoxic dose of the drug “Avizuril” when administered orally on the general functional parameters of experimental rats noted suffocation and depression of the central nervous system, the death of most animals during the first day. Subsequently, the behavior of the surviving animals was characterized by suppression of motor reactions during the next 24–72 hours, decreased motor activity, agitation, reactivity and aggression, movement disorders, decreased response to touch and pain. According to the Sanitary and hygienic norms and SOU 85.2-37-736: 2011 according to the toxicity class the drug “Avizuril” in the concentration of 2.5 % when administered to the stomach of white rats belongs to the third class of danger (moderately dangerous compounds). In the future, it is planned to study the allergic properties of the drug “Avizuril”.

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Section: матеріал і методи дослідженьunclassified

Determination of acute toxicity of antiprotozoal drug “Avizuril”

Hunko

Фотіна

2022

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“…An essential stage in developing new veterinary drugs is the determination of their safety and effectiveness, which includes conducting a wide range of preclinical studies (Venkatesan & Ramanathan, 2017;Vasylyev et al, 2021;Karpenko et al, 2022;Martyshuk et al, 2022). Special attention is paid to the long-term use of the researched means.…”

Section: Introductionmentioning

confidence: 99%

Comparative assessment of various methods of studying the skin toxicity of a wound-healing drug

Kushnir¹,

Kushnir²,

Patereha³

et al. 2022

Ukr. Jour. of Vet. and Agr. Sci.

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The article presents the results of studying the subacute skin toxicity of a wound-healing cream based on betamethasone dipropionate, gentamicin sulfate, and clotrimazole. According to the Organization for Economic Cooperation and Development (OECD No. 410), the research was conducted using the classic method. When studying the effect of a wound-healing agent on the body of animals during long-term 28-day dermal application by the classical method in animals of the I, II, and III experimental groups, which received the drug in a dose of 0.5, 2.5, and 5 ml/kg body weight; respectively no significant changes were found in the body weight of the animals and the weight coefficients of the liver, heart, spleen, kidneys, and lungs. At the same time, in the animals of the II and III research groups, a slight increase in the concentration of hemoglobin was noted, respectively, by 1.3 and 3.9 %, the level of urea – 5.3 and 11.2 %, the activity of AST – 9.8 and 14.9 % compared to the indicators of animals of the control group. In these groups, there was a decrease in total protein concentration by 5.5 and 6.8 %, creatinine level by 3.1 and 5.3 %, and ALT activity by 6.5 and 9.7 %. The studies conducted according to the OECD No. 410 make it possible to obtain more informative data on the toxic effect of the investigated agent. In particular, it was established that the use of the researched drug in animals of the I, II, and III experimental groups caused a decrease in the weight coefficients of the spleen mass, respectively, by 19.1 (Р < 0.05), 22.4 (Р < 0.05) and 28.3 % (P < 0.05), hearts – 3.6, 4.6 and 7.7 %, kidneys – 4.9, 6.5 and 10.4 % and animal body weight – 4.5, 5.4 and 6.4 %, hemoglobin concentrations – 2.6, 2.9 and 4.4 %, leukocyte counts – 21.4, 16.1 and 15.1 %, hematocrit values – 1.9, 3, 6 and 4.0 %. The average hemoglobin content in the erythrocyte (MSN) also decreased by 8.3, 6.9, and 5.1 %, and the average erythrocyte (MCV) volume was 5.0, 4.7, and 1.7 %. In addition, an increase in weight coefficients of liver mass was established by 10.8 (P < 0.05), 11.8 (P < 0.05), and 15.6 % (P < 0.05). When studying the effect of the researched agent during 28-day dermal application on biochemical indicators of blood serum in animals of the first experimental group, a decrease in the concentration of total protein by 5.8 % was established. Under these conditions, an increase in creatinine level, urea level, ALT, and AST was established, respectively, by 6.2, 18.8 (P < 0.05), 3.8, and 14.7 % (P < 0.05). It should be noted that the use of the researched product in animals of the II and III experimental groups caused an increase in the level of urea, respectively, by 28.6 and 35.7 % (Р < 0.05), creatinine by 8.4 and 3.5 %, AST – 16.4 (P < 0.05) and 11.3 % and the activity of ALT – 8.5 and 11.0 %.

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“…One of the most critical stages of the preclinical evaluation of veterinary medicinal products is the study of their specific activity and harmlessness (Sachuk et al, 2019;Zazharskyi et al, 2020;Martyshuk et al, 2022;Karpenko et al, 2022;Varkholiak et al, 2022). To carry out this stage of pharmaceutical development, models and methods are used taking into account the requirements of the Law of Ukraine "On Veterinary Medicine" and the Directive of the Commission of July 23, 1991, on the principles and working instructions of good manufacturing practice for veterinary drugs (91/412/EEC).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological studies of the veterinary medicinal product “Dibutalastin Ointment”

Кацараба

Сачук

Gutyj

et al. 2022

Ukr. Jour. of Vet. and Agr. Sci.

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The study of pharmacological studies of the veterinary medicinal product for external use in the form of ointment – “Dibutalastin Ointment” is a mandatory stage of preclinical research of the drug, which is a new development of PP “Biopharm” and LLC “DEVIE”. In a scientific experiment on laboratory animals, it is possible to assess the drug's safety for different terms of use to determine the zone of toxic action and doses that do not cause harmful effects on health. Therefore, the work aimed to carry out pharmacological studies of the drug with methyl salicylate and dimethyl sulfoxide in the form of an ointment for treating European fallow deer, deer, dogs, and cats with mastitis, arthritis, myositis, and injuries of various origins. The toxicological characteristics of the studied ointment “Dibutalastin” based on methyl salicylate and dimethyl sulfoxide were studied in an "acute" study on warm-blooded animals. The average lethal dose (LD50) for intragastric administration could not be established, as the volume exceeded the permissible level. It was established that according to the “average lethal dose when entering the stomach” indicator, the veterinary medicinal product belongs to relatively non-toxic substances (toxicity class IV). The results of pharmacological studies indicate the absence of resorptive-toxic effects, sensitizing properties, and irritating effects on the mucous membranes of the eyes and skin. Pathomorphological studies of animal organs when studying the acute toxicity of the drug showed that the developed ointment with methyl salicylate and dimethyl sulfoxide does not cause pathological changes in internal organs. From the point of view of veterinary toxicology, this drug is safe. Further studies will be the next stage of pre-registration tests aimed at studying the embryotoxic effect of “Dibutalastin Ointment”, which is mandatory material of the “Safety and residue studies” section of the dossier for this medicinal product.

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Advanced research for physico-chemical properties and parameters of toxicity piperazinium 2-((5-(furan-2-YL)-4-phenyl-4H-1,2,4-triazol-3-YL)THIO)acetate

Cited by 31 publications

References 9 publications

Determination of acute toxicity of antiprotozoal drug “Avizuril”

Determination of acute toxicity of antiprotozoal drug “Avizuril”

Comparative assessment of various methods of studying the skin toxicity of a wound-healing drug

Pharmacological studies of the veterinary medicinal product “Dibutalastin Ointment”

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