scholarly journals Preclinical evaluation of the veterinary drug “Amoxidev 15” for its use in surgical and obstetric practice

2021 ◽  
Vol 23 (103) ◽  
pp. 109-115
Author(s):  
L.-M. Kostyshyn ◽  
R. Sachuk ◽  
Ye. Kostyshyn ◽  
O. Katsaraba

Suspension for injection “Amoxidev 15” is prescribed to fur-bearing animals (mink, fox), dogs and cats for the treatment of respiratory diseases (tonsillitis, tracheitis, pneumonia, bronchitis, rhinitis, sinusitis, bronchopneumonia), digestive (gastritis, enteritis, enteritis). genitourinary systems (nephritis, urethritis, urocystitis, mastitis, metritis, agalactia), musculoskeletal system (arthritis, osteoarthritis, joint injuries, tendonitis, hoof lesions), skin and soft tissues (eczema, dermatitis) caused by sensitive drug by microorganisms, including colibacillosis, streptococcus, bronchopneumonia, etc. Toxicological evaluation of the veterinary drug “Amoxidev 15” under the conditions of acute and subacute toxicological experiments on a model of white rats. According to the results of an acute toxicological experiment with intragastric administration of the drug “Amoxidev 15” white rats DL50 could not be calculated because the death of laboratory animals was not detected within 14 days after administration. The maximum administered dose (in absolute weight of the drug) was 20000.0 mg/kg body weight, which allows to refer the drug to class VI toxicity of relatively harmless substances (DL50 > 15000 mg/kg body weight), and the degree of safety to class IV – low-hazard substances (DL50 > 5000 mg/kg). According to the results of an acute toxicological experiment with subcutaneous administration of the drug “Amoxidev 15” white rats DL50 could not be calculated because the death of laboratory animals was not detected within 14 days after administration, the maximum dose was 5000.0 mg/kg body weight, therefore, the drug “Amoxidev 15” when administered subcutaneously by toxicity can be classified as class VI substances relatively harmless (DL50 Subcut > 4500.0 mg/kg). When administered subcutaneously to white rats, the drug “Amoxidev 15” under conditions of subacute toxicological experiment in doses of 0.1–1.0 ml/kg does not cause hemo-, hepato- and nephrotoxic effects on the body of laboratory animals, although 3-day administration of the drug in a dose 1.0 ml/kg body weight caused an increase in the activity of hepatospecific enzymes ALT and AST by 12.5 and 11.1 % (P < 0.05), respectively, relative to the control, which was restored to the control level 7 days after cessation.

Author(s):  
R. M. Sachuk ◽  
S. V. Zhyhalyuk ◽  
I. M. Lukyanik ◽  
M. S. Mandyhra ◽  
Ya. S. Stravsky ◽  
...  

The purpose of the work was to determine, in experiments on rodents, the parameters of acute toxicity, allergenic and locally irritative effects of iodine-containing uterine drug for the treatment and prevention of intrauterine infections of animals. Materials and methods. Preclinical studies of acute toxicity of “Yodosol” containing iodine and potassium iodide were performed on 90 white mice, 30 white outbred rats and 6 rabbits. Clinical, pharmacotoxicological and statistical methods were used. Results of work. It has been found that at intragastric administration in experimental rats and mice, DL50 values exceed 8,000 mg/kg body weight and have no effect on the behavioral responses and physiological parameters of laboratory animals. It has been investigated that “Yodosol” aerosol has no local toxic and irritant effects on the skin and mucous membranes of laboratory animals (rabbits). Conclusions. The use of the drug «Yodosol», in doses above 8,000 mg/kg body weight, does not affect the behavioral responses and physiological parameters of laboratory animals. The drug has no local toxic and irritant effects on the skin and mucous membranes. According to the requirements of SOU 85.2-37-736:2011 and GOST 12.1.007-76, the newly developed drug “Yodosol” belongs to low-toxic substances — 4 toxicity classes


2018 ◽  
Vol 20 (92) ◽  
pp. 117-120
Author(s):  
V. D. Ishchenko ◽  
A. M. Shevchenko ◽  
N. M. Slobodyuk ◽  
R. O. Vasiv ◽  
H. V. Yarova ◽  
...  

Antibiotic resistance of the main infectious disease pathogens is one of the biggest problems of present time, which causes the need for searching for new antimicrobial medicinal substances and developing effective medicinal agents. One of the innovative medicinal preparations with the antimicrobial action, which is recommended for application for animals with hoof diseases, is ForticeptTM Hoof Oinment. Integration in the practice new medicinal preparations needs their strict toxicological control, which involves the exploring of acute and chronic toxicity and remote effects of possible side effect. The purpose of work was the determination of the acute toxicity parameters of the ForticeptTM Hoof Oinmentduring the oral administration to white laboratory mice and evaluation of the skin resorptive action of the preparation after it was administrated on rats’ skin. For determination of the acute toxicity there were used male laboratory mice with the average weight of the body 20 g – two groups with 10 animals in each. For the first group (the control one) with the help of the probe there was injected the distilled water (0.1 ml) into stomach. For the second group there was injected ForticeptTM Hoof Oinment (0.1 g), where the dose of the preparation is equal 500 mg/kg. For evaluation of the skin resorptive action of the preparation there were used 6 white rats with the average weight of the body 175 g. On the pre-prepared patch of skin there was administrated the preparation in the number that is equal 2857 mg/kg of body weight. For control there was leaved a free from preparation patch of bare skin. Exposition lasted for 4 hours. The indicators were explored in dynamics after 6, 24, 48 hours from the exposition started. After the research results there was established that ForticeptTM Hoof Oinment doesn’t cause death after its intragastric administration to the white laboratory mice in the number that is equal 5000 mg/kg of the body weight, that’s why depending on the degree of toxicity it belongs to the V toxicity class (Practically nontoxic). After one-time application of the preparation to the white rats in the number which is equal 2857 mg/kg of the body weight there wasn’t observes no death or pronounced changes in the behavior reactions, motor activity, state of the nervous system, amount of the consumed food and water. Therefore ForticeptTM Hoof Oinmentaccording to the results of the determination of the acute toxicity after its administration on the skin to the white rats depending on the degree of toxicity it belongs to the V toxicity class (Practically nontoxic). ForticeptTM Hoof Oinment doesn’t detect skin resorptive action, that points on the absence of toxic effects of the preparation due to its application on the skin.


2020 ◽  
Vol 22 (100) ◽  
pp. 28-31
Author(s):  
Yu. R. Hunchak ◽  
B. V. Gutyj ◽  
R. M. Sachuk ◽  
Ya. S. Stravsky

In the study of the drug for injectable use – “Devimectin 1 %”, together with the confirmation of therapeutic properties, it is necessary to determine the LD50 obtained in the study of acute toxicity. The aim of the work was to study the acute toxicity of “Devimectin 1 %” in white rats by injection. To fulfill this goal on the principle of analogues was formed control and three experimental groups of 4 animals each (n = 4). The drug was administered in doses of 5000.0; 10000.0; 20000.0 mg/kg body weight in absolute weight of the drug once subcutaneously in the withers. The control animals were injected subcutaneously with sterile saline 1.0 cm3. After taking into account the results of the previous experiment in the main experiment, 7 experimental groups were formed, whose rats were injected subcutaneously with “Devimectin 1 %” in doses of 5000.0; 7500.0; 10000.0; 12500.0; 15000.0; 17500.0 and 20000.0 mg/kg body weight, as well as a control group to which animals were injected with sterile saline with a volume of 1.0 cm3. There were 6 animals in each group (n = 6). It was found that for the administration of the drug at a dose of 5000 mg / kg body weight, no animal died, for 10000.0 and 20000.0 mg/kg body weight, respectively, one and 4 animals died. Death occurred for 2–6 days depending on the administered dose. In the main experiment with subcutaneous administration of “Devimectin 1 %” at a dose of 5000.0 mg/kg body weight during the 14-day period of the study, no animal died; for the introduction of the drug at a dose of 7500.0 mg/kg killed one animal; for 10000.0 – 2; for 12500.0 and 15000.0 – 3 rats; for 17500.0 – 5 rats and for the introduction of the drug at a dose of 20000.0 mg/kg body weight, all experimental animals died. The death of laboratory animals occurred for 2–6 days depending on the administered dose. According to the results of studies, it was found that the LD50 of the drug “Devimectin 1 %” under the conditions of its single subcutaneous administration to female rats is 12881.20 ± 1390.54 mg/kg, LD10 – 5978.43 mg/kg, LD16 – 7495.68 mg/kg, LD84 – 18266.73 mg/kg, LD90 – 19783.98 mg/kg, LD100 – 20959.49 mg/kg body weight, respectively. Therefore, the drug “Devimectin 1%” when administered subcutaneously can be classified as toxicity class VI – substances relatively harmless (LD50subcut> 4500,0 mg/kg). Further studies will be the next step in pre-registration trials to examine the subacute toxicity of “Devimectin 1 %”.


2010 ◽  
Vol 30 (7) ◽  
pp. 725-735 ◽  
Author(s):  
Bernard D Goldstein

Epidemiological findings suggesting that formaldehyde exposure is associated with a higher risk of acute myelogenous leukemia (AML) and other hematological cancers have led to consideration of the potential mechanism of action by which inhalation of this rapidly reactive agent can cause bone marrow cancer. Two major mechanism-based arguments against formaldehyde as a leukemogen have been the difficulty in envisioning how inhaled formaldehyde might penetrate to the bone marrow; and the lack of similarity of non-cancer effects to other known human myeloleukemogens, particularly the absence of pancytopenia in humans or laboratory animals exposed to high levels. However, both of these arguments have been addressed by the recent finding of a pancytopenic effect and chromosomal abnormalities in heavily exposed Chinese workers which, if replicated, are indicative of a genotoxic effect of formaldehyde on hematopoietic stem cells that is in keeping with other known human leukemogens. Review of the body of evidence suggests an apparent discrepancy between studies in laboratory animals, which generally fail to show evidence of penetration of formaldehyde into the blood or evidence of blood or bone marrow genotoxicity, and studies of exposed humans in which there tends to be evidence of genotoxicity in circulating blood cells. One possible explanation for this discrepancy is species difference. Another possible explanation is that myeloid precursors within the nasal mucosa may be the site for leukemogenesis. However, chloromas, which are local collections of myeloid tumor cells, are rarely if ever found in the nose. Other proposed mechanisms for formaldehyde leukemogenesis are reviewed, and dose issues at the interface between the epidemiological and hematotoxicological findings are explored.


2020 ◽  
Vol 99 (11) ◽  
pp. 1276-1279
Author(s):  
Valery N. Rakitskii ◽  
Tatiana M. Epishina ◽  
Elena G. Chkhvirkiya

Introduction. Historically, pesticides are evaluated more strictly from a medical point of view than other chemicals. Since their features, such as deliberate introduction into the environment, the possibility of contact with them by large masses of the population, and the high biological activity determine their potential danger to humans. Purpose of research - study of the biological effect of a technical product derived from triazoles when it is repeatedly ingested orally in mammals (rats), establishment of inactive and active doses, justification of the permissible daily dose (DSD) for humans. Material and methods. In acute experiments, white rats were used, including 6 animals in the group. Tested dose: 500-4000 mg/kg of body weight. A chronic (12 months) experiment was performed on 80 male rats with a bodyweight of 180-190 g at the beginning of the study. Tested doses: 5.0; 16.0 and 55.0 mg/kg of body weight (1 control and 3 experimental animals, 20 individuals each). In the dynamics of the experiment, we observed the condition and behavior of animals, water, and food consumption, recorded the timing of death, changes in body weight, physiological, biochemical, and hematological indices. Results. Indices of the acute oral toxicity on the studied product LD50 male rats were 2250 ± 483 mg/kg body weight. The dose of 5.0 mg / kg of body weight was not found to cause significant changes in all studied indices. The doses of 16.0 and 55.0 mg/kg of body weight had a polytropic effect on the body in experimental animals. Discussion. The studied product for the acute oral toxicity refers to low-hazard compounds, the doses of 16.0 and 55.0 mg/kg of body weight has a polytropic effect on the mammalian body, causing changes in carbohydrate, lipid, and lipoprotein metabolism in the body of rats - was accepted as acting. The dose of 5.0 mg / kg of body weight, when administered in rats, there are no changes in all the studied parameters throughout the experiment, is accepted as invalid. Based on the inactive dose-5.0 mg/kg of body weight and taking into account the reserve factor of 100, we have scientifically justified DSD for a person at the level of 0.05 mg/kg. Summary. The conducted sanitary and Toxicological studies indicate the need to assess the toxicity of new technical products to the mammalian body, to increase the reliability of the developed hygiene standards in environmental objects and food products.


Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2590
Author(s):  
Dhondup Namgyal ◽  
Kumari Chandan ◽  
Sher Ali ◽  
Ajaz Ahmad ◽  
Maha J. Hashim ◽  
...  

In the modern research field, laboratory animals are constantly kept under artificial lighting conditions. However, recent studies have shown the effect of artificial light on animal behavior and metabolism. In the present study on mice, following three weeks of housing in dim light at night (dLAN; 5lux) and complete darkness (DD; 0lux), we monitored the effect on body weight, daily food intake, anxiety-like behavior by employing the open field test, and expression of the period (PER1) gene. We also studied the effect of oral administration of different concentrations of curcumin (50, 100, and 150 mg/kg) for three weeks in the same mice and monitored these parameters. The exposure to dLAN had significantly increased the anxiety-like behavior and body weight possibly through the altered metabolism in mice, whereas exposure to DD caused increased anxiety but no significant difference in weight gain. Moreover, the expression of the PER1 gene involved in sleep was also found to be decreased in the aberrant light conditions (dLAN and DD). Although the treatment of curcumin had no effect on body weight, it ameliorated the anxiety-like behavior possibly by modulating the expression of the PER1 gene. Thus, alteration in the light/dark cycle had a negative effect on laboratory animals on the body weight and emotions of animals. The present study identifies the risk factors associated with artificial lighting systems on the behavior of laboratory animals and the ameliorative effects of curcumin, with a focus on anxiety-like behavior.


Author(s):  
Roman Sachuk ◽  
Yaroslav Stravskyy ◽  
Bogdan Gutyj ◽  
Tetiana Velesyk ◽  
Orest Katsaraba ◽  
...  

«Kolidev 8M» (powder for oral use) is a veterinary drug used to treat ornamental birds (pheasants, peacocks) in diseases of the digestive tract caused by microorganisms sensitive to colistin. In the study of the drug «Kolidev 8M» for oral administration, along with the confirmation of therapeutic properties, it is necessary to determine the LD50 obtained in the process of studying acute toxicity. The aim of research. The aim of research was to determine the acute toxicity of the veterinary drug «Kolidev 8M» (powder for oral administration) under the conditions of intragastric administration to white mice. Materials and methods of research. To achieve this aim, an experiment was conducted on 114 males of nonlinear white mice kept under optimal conditions in the vivarium of DEVIE LLC (Rivne, Ukraine). In the first series of experiments on the principle of analogues was formed control and three experimental groups of 6 animals each (n=6). The drug in the form of a solution was administered once orally using a esophageal gastric tube in doses of 500,0; 2000,0 and 4000,0 mg/kg body weight by absolute weight of the drug. The animals of the control group were injected with distilled water. After taking into account the results of the first experiment in the next experiment, 6 experimental groups were formed – mice, which were administered the drug «Kolidev 8M» in the form of a solution in doses (by absolute weight of the drug) – 500,0; 1000,0; 1500,0; 2000.0; 2500,0; 3000,0; 3500 and 4000,0 mg/kg body weight, as well as the control group – animals that were injected with distilled water with a volume of 0.5 cm3 according to similar regulations (Zapadniuk, 1983; Kotsiumbas, 2005; Karkyshchenko & Hrachev, 2010). There were 6 animals in each group (n=6). After their death, a pathological autopsy was performed (Zharov A. et al., 2003). The average lethal dose of LD50 was calculated by the method of probit analysis by Prozorovsky V.B. Research results. According to the results of research, it was found that the LD50 of the drug «Kolidev 8M» (powder for oral administration) under the conditions of its single intragastric administration to male mice is 2024,72±232,45 mg/kg, LD10 – 392,87 mg/kg, LD16 – 751,56 mg/kg, LD84 – 3297,88 mg/kg, LD90 – 3656,57 mg/kg, LD100 – 3934,47 mg/kg body weight, respectively. According to the results of an acute toxicological experiment with intragastric administration of the drug «Kolidev 8M» to white male mice, LD50 was 2024,72±232,45 mg/kg body weight. This allows, according to toxicity, to refer this drug to class IV – low-toxic substances (LD50 501,0-5000,0 mg/kg body weight), and the degree of danger to class III – moderately safe substances (LD50 151,0-5000,0 mg/kg body weight). Conclusions and prospects for further research. The drug «Kolidev 8M» in terms of toxicity belongs to class IV – low-toxic substances, and the degree of danger to class III – moderately safe substances. Further studies will be the next stage of pre-registration trials aimed at studying the subacute toxicity of the drug «Kolidev 8M»


2021 ◽  
Vol 10 (2) ◽  
pp. 101-105
Author(s):  
Yu. M. Domnina ◽  
V. V. Suslov ◽  
S. A. Kedik ◽  
D. A. Akhmedova ◽  
A. P. Malkova

Introduction. Acute toxicity of naltrexone hydrochloride nasal spray during intragastric administration to mice and local irritant effect on rabbits was studied. At all stages of the experiment, observations were made on the General condition of the animals. The state of homeostasis was evaluated using functional, hematological and morphometric methods. According to the results of research, there was no local irritant effect on the eyes of rabbits, as well as no toxic effect of high doses of the drug on animals. Introduction. Naltrexone hydrochloride in doses of 1.5– 5 mg/day has shown its effectiveness in the treatment of a number of diseases. Due to the lack of such a "low-dose" naltrexone registered on the pharmaceutical market, we have developed the composition of the nasal spray naltrexone hydrochloride. One of the stages of our research is to study the safety of the drug being developed. The first step in this direction was to study its acute toxicity and local irritant effect.Aim. Study of acute toxicity and local irritant effect of naltrexone hydrochloride nasal spray.Materials and methods. The object of the study was a nasal spray of naltrexone hydrochloride. Acute toxicity studies were performed on outbred adult mice (females). Study of local irritant effect on Soviet chinchilla rabbits (males).Results and discussion. The study of acute toxicity showed that the drug, at a dose significantly higher than the estimated maximum daily therapeutic dose for humans, did not have a significant toxic effect on the body of laboratory animals. The presence of a local irritant effect in the studied drug was not established in the framework of the experiment.Conclusion. As part of the experiment, the drug under study did not have a local irritant or toxic effect on the animal body. The results obtained allow us to continue the development and study of the nasal spray naltrexone hydrochloride.


2019 ◽  
Vol 19 (1) ◽  
pp. 6
Author(s):  
Nabila S Petta ◽  
Edwin De Queljoe ◽  
Rooije R.H. Rumende

PENGARUH PEMBERIAN EKSTRAK ETANOL KEMBANG SEPATU (Hibiscus rosa-sinensis L.) TERHADAP JUMLAH SPERMATOZOA, BERAT BADAN, DAN       BERAT TESTIS TIKUS JANTAN WISTAR (Rattus norvegicus)ABSTRAKPenelitian ini bertujuan untuk mengetahui pengaruh pemberian ekstrak etanol kembang sepatu terhadap jumlah spermatozoa tikus jantan wistar (Rattus norvegicus). Penelitian ini menggunakan rancangan acak lengkap (RAL) dengan menggunakan 24 ekor tikus putih jantan galur wistar (Rattus norvegicus) yang dibagi atas beberapa kelompok dimana kelompok 1 sebagai kelompok kontrol tanpa perlakuan, kelompok 2, 3 dan 4 sebagai kelompok perlakuan dengan dosis secara berturut-turut 3,6 mg/ml; 7,2 mg/ml; dan 14,4 mg/ml. Perlakuan diberikan secara oral sekali sehari sebanyak 1 ml selama 50 hari sesuai siklus spermatogenesis. Variabel yang diamati yakni jumlah sel spermatozoa, berat badan, dan berat testis. Hasil penelitian ini menunjukkan bahwa ekstrak etanol kembang sepatu dapat menurunkan jumlah sel spermatozoa, serta menyebabkan adanya perbedaan berat badan dan berat testis namun, berdasarkan hasil analisis varians, ekstrak etanol daun kembang sepatu tidak dapat menurunkan jumlah sel spermatozoa, berat badan dan berat testis tikus putih jantan galur wistar (Rattus norvegicus) secara signifikan.Kata Kunci: Sel spermatozoa, Kembang sepatu (Hibiscus rosa-sinensis L.),                    Tikus jantan Wistar (Rattus novergicus) THE INFLUENCE OF THE ETHANOL EXTRACTS  OF GRANTING HIBISCUS (Hibiscus Rosa-sinensis L.) AGAINST THE NUMBER OF SPERMATOZOA, WEIGHT AND THE WEIGHT OF THE TESTES MALE WISTAR RATS (Rattus norvegicus) ABSTRACTThis research’s objective is to know the influence of injecting ethanol extract from a hibiscus into a number of common male rats (Rattus norvegicus). This research uses the approach of complete randomized design (CRD) onto 24 common white rats (Rattus norvegicus) that is divided into groups, where group 1’s approach is control without treatment, groups 2, 3, and 4’s approach is with treatment, with consecutive doses being 3.6 mg/ml; 7.2 mg/ml; and 14.4 mg/ml.  The treatment is induced orally as large as 1cc per day for a total of 50 days following the spermatogenesis cycle. The variables that are being observed are the amount of spermatozoon cells, body weight, and testicle weight. The results of this research indicates that ethanol extract from hibiscuses, from a quantity perspective, can decrease spermatozoon cells, and it may also influence the body weight and testicle weight of the subject, in this case are common rats (Rattus norvegicus) but, from the mathematical results from Analysis Of Variance, ethanol extract from the leaves of a hibiscus cannot decrease the amount of spermatozoon, body weight, and testicle weight  of a common white rat (Rattus norvegicus).Keywords: Spermatozoon Cells, Hibiscus (Hibiscus rosa-sinensis L.), Common (white) rat (Rattus novergicus)


2020 ◽  
Vol 22 (97) ◽  
pp. 130-135
Author(s):  
V. B. Dukhnitsky ◽  
I. M. Derkach ◽  
S. S. Derkach ◽  
I. O. Fritsky ◽  
M. O. Plutenko ◽  
...  

During the preclinical studies of new drugs, the study of the degree of manifestation of their irritant and allergenic effects affects subsequent clinical studies, for example the routes of administration, the need to add excipients to reduce irritation. The article presents the results of studies of the irritant effects and allergenic properties of the Iron in rare unconventional valence – IV. The irritant effect of the Iron(IV) clathrochelate complexes on the skin was studied comprehensively. 20 rabbits were divided into 4 groups (control and three experimental), 5 animals each. The  ointment on the vaseline and aqueous solution of the Iron(IV) clathrochelate complexes was applied to the skin of rabbits of the experimental groups. Also this solution was introduced subcutaneously. The investigated dosage forms were used at a dose of 1 ml/kg body weight (based on the active ingredient 500 mg/kg body weight of the laboratory animal). The results of the studies showed that of the Iron(IV) clathrochelate complexes has no irritant properties when used externally and is characterized by a lack of local reaction by subcutaneous injection. Determination of allergenic properties was performed by detecting itching and swelling in the guinea pigs in animals which were sensitized with this substance. In addition, in order to assess the severity of the inflammatory reaction, the skin temperature was determined before the experiment and on the 20th day of the experiment, and the skin fold thickness was measured using a caliper. The results of the studies showed that there is no allergic action of the Iron(IV) clathrochelate complexes. The results of the ophthalmic test on laboratory animals confirmed the data obtained.Therefore, comprehensive studies of the irritant and allergenic effects of the Iron(IV) clathrochelate complexes were performed for the first time. The Iron(IV) clathrochelate complexes in the form of ointment and solution does not irritate the skin and mucous membranes and has no allergenic properties to the body of the laboratory animals.


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