scholarly journals Study of acute toxicity of the drug «Kolidev 8M» with a single intragastric injection in laboratory animals

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»

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 ◽  
pp. 69-76
Author(s):  
A. Doroshenko

The emerging and steady increase of microbes that are resistant to antimicrobial treatments has become a global public health concern that threatens the effective treatment of infectious diseases, therefore, the development of new medicines with antimicrobial properties is one of the priorities of the health systems. Cationic detergents, which, as a result of the combination of their surface activity and bactericidal properties, are promising for use in pharmacy and medicine. One of the representatives of the cationic surfactant group is polyhexamethylene guanidine hydrochloride (PGMG-GC) which was shown to be less toxic compared to some other disinfectants and effective against a wide spectrum of microbes. The aim of the study was to determine the acute toxicity parameters of a highly-dispersive silica (HDS) and PGMG-GC composite in mice after intragastric administration. The study was carried out on 23 BALB/c female mice weighing 18–22 g. To determine the toxicity, the animals were divided into the following groups. The first group was intragastrically injected with a composite of HDS and PGMG-GH, the second group was given a suspension of HDS, the third group was given a solution of PGMG-GC, and the fourth (control) group was treated with water for injection. The mass of the animals was determined before and on the 3rd, 7th, and 14th day after the composite administration. Administration of PGMG-GC or PGMG-GC + HDS composite caused significant decrease in body weight at 3rd and 7th day compared to control with further normalization on day 14. No significant changes of body weight were found in HDS group. No death of mice occurred after a single intragastric injection of the HDS + PGMG-GC composite during 14 days of the study. For the solution of PGMG-GC (without HDS), lethal cases were reported 2 h after the treatment at a dose level of 400 mg/kg. The condition of the animals survived normalized and, by the day 14, it corresponded to that in the control group for the most of the signs of toxicity indicating the reversibility of the toxic effect of PGMG-GC. Therefore, PGMG-GC is less toxic whet it is used as a part of the composite. Since no lethal cases were reported after a single intragastric administration of the composite at a dose of 2 000 mg/kg of body weight, the composite HDS + PGMG-GC appears to be low toxic according to the classification of substances by toxicity.


2019 ◽  
Vol 21 (95) ◽  
pp. 47-54
Author(s):  
M. I. Zhyla ◽  
I. P. Patereha ◽  
E. Tomaszewska ◽  
S. Muszynski ◽  
P. Dobrowolski ◽  
...  

The article presents the study results of the acute and subacute toxicity of the veterinary drug “Tylmozyn 25” (solution for oral administration) based on tilmicosin. Intra-gastric administration of “Tylmozyn 25” to white mice at a dose of 25000 mg/kg of body weight caused the death of 100% of the animals, a dose of 15000 mg/kg of body weight caused the death of 66% of the white mice. The average time of death was 2 and 5 hours correspondingly. While determining the toxicity of “Tylmozyn 25” in white rats, we did not spot the death of any studied animal at any administered dose (5000, 15000, 25000 mg/kg of body weight). Based on the result of our study, we conclude that the veterinary drug Tylmozyn 25 belongs to the fourth of toxicity class – low toxic substances. LD50 of Tylmozyn 25 in white mice is 14167 mg/kg, while in white rats LD50 is higher than 25000 mg/kg. Testing on white rats intra-gastric drug “Tylmozyn 25” during for 14 days, both in therapeutic (80 mg/kg of body weight) and 10-fold doses (800 mg/kg of body weight) did not cause animal death, but caused a decrease in body weight, a significant decrease in the coefficients of weight of the liver and spleen and a tendency to increase the coefficients of weight of the heart and lungs compared with the animals of the control group. Animals which got the drug at a dose of 800 mg/kg of body weight showed erythrocytosis, leukopenia, increased enzymatic activity of AST, ALT, and LDH, the content of total protein against to decrease urea and creatinine, which may indicate impaired liver, kidney function and hematopoietic organs. The macroscopic and microscopic structure of the internal organs of the experimental rats is preserved. Rats receiving a tenfold therapeutic dose of the drug for 14 days, histologically revealed the most granular protein dystrophy in the liver and kidneys, which was manifested by discomplexation of the lamellae, presence of hepatocytes with uneven granular cytoplasm, slightly colored cytoplasm, hypertrophied nuclei, renal convoluted tubules and narrowing of their lumen, compaction of the mesh of the renal corpuscle. In the myocardium, the branching, swelling of the muscle fibers, swelling of the stroma with cell infiltrates, mainly of the lympho-histiocytic series, was observed, which indicated the development of serosa myocarditis. Structural changes in the liver, kidneys and heart were confirmed by biochemical parameters of the enzymatic activity of the serum of rats of this group.


2019 ◽  
Vol 2 (2) ◽  
pp. 41-44
Author(s):  
O. L. Nechyporenko ◽  
A. V. Berezovskyy ◽  
H. A. Fotina ◽  
R. V. Petrov ◽  
T. I. Fotina

An important element in ensuring the epizootic well-being of the poultry industry is disinfection. Modern poultry farming requires a large number of effective disinfectants. It is known that the resistance of microorganisms to the effects of disinfectants is based on a genotypic mechanism. The nature of the formation of resistance to disinfectants and antiseptics is different than antibiotics. With regard to disinfectants, resistance is formed more slowly and the proportion of resistant strains in the population of microorganisms may not be high for a long time. This is due to different mechanisms of formation of resistance to antibiotics and disinfectants, in the first case – plasmid mechanism, in the second – chromosomal. However, increasing the resistance to the active substance in disinfectants can be widespread, so it is necessary to periodically rotate disinfectants. The goal of the work – to investigate the parameters of acute toxicity of the disinfectant biocide “Zodizin”. The studies were conducted in the laboratory of Veterinary Pharmacy and the Vivarium of Sumy National Agrarian University. The drug “Zodizine” contains: polyhexamethyleneguanidine hydrochloride – 21.0 %, alkylldimethylbenzylammonium chloride – 3.0 %. For toxicological examination of the disinfectant, healthy white male rats and white female rats weighing 200 ± 10 g 1.5 years of age were used. In the study of acute toxicity of animals observed daily, noted the general condition of the animals, features of their behavior. Studies have found that the toxic effect of the disinfectant “Zodizin” clinically manifested almost equally in both males and females. The average lethal dose for the rat female was 1000.0 ± 35.0 mg/kg body weight, males 1033.0 ± 34.3 mg/kg. Therefore, according to the classification of substances by toxicity, the drug by intragastric administration can be attributed to low-toxic substances. Observations on animals revealed that 1–3 hours after oral administration of the drug in a subtoxic dose in laboratory animals, shortness of breath and inhibition of the central nervous system were noted. Most of them died during the first day. Subsequent observations of the surviving animals indicated that their motor response was suppressed over the next 24–72 hours. Conclusions and prospects for further research: 1. It was found that the average lethal dose of the drug “Zodizin” with oral administration to rats-females was 1000.0 ± 35.0 mg/kg body weight, males – 1033.0 ± 34.3 mg/kg. 2. Experimental studies have proved that the disinfectant “Zodizin” according to GOST 12.1.007-76, belongs to the IV class of danger, that is, to the low-dangerous compounds, and according to GOST 12.1.07 – to the III class of hazard of substances and can be used for disinfection premises where animals and poultry are kept. Further, the sporoсide and corrosion properties of the “Zoodizin” biocide will be studied.


2017 ◽  
Vol 19 (74) ◽  
pp. 20-23
Author(s):  
Yu. V. Loboiko ◽  
M. M. Danko ◽  
O. V. Krushelnytska ◽  
S. I. Kravets

The paper presents the results of research to determine the parameters of acute toxicity of «Brovermectin-granulate». The material for the study of acute toxicity were of carp earlings. In experiment used drug «Brovermectin-granulate» (1 g of the drug contains: active actiion substance ivermectin – 3.5 mg, tocopherol acetate – 20 mg). The introduction of the drug  was carried out orally using a probe in anterior intestine of fish. The drug was administered to fish in the form of a homogeneous suspension produced 1 % starch solution individually, in doses of 1000, 4000, 8000, 12000, 16000 and 20000 mg/kg of body weight. For settings acute toxicity determined the general condition and death of fish; for a dose of the drug (DL50) calculated by methods G. Kerber, H. Pershyn, least squares analysis of probit mortality curves for V.B. Prozorovskyj, means three points for B.M. Shtabskyj. At this stage of research it was found lethal (DL100) and maximum tolerated (DL0) dose of «Brovermectin-granulate» for earlings carp. As a result of studies found that 100% death of fish following the dose of 20000 mg/kg (DL100), and for the drug at a dose of 4000 mg/kg (DL0) set to survival of 100% fish. Established that the value of average lethal dose of «Brovermectin-granulate» for fish regardless of the method of calculation mainly coincided and were 10932,8–11200 mg/kg for earlings carp. Thus, the drug «Brovermectin-granulate» for oral administration to fish belongs to grade 4 toxicity – low toxic substances.


Author(s):  
Michel Archange Tagne Fokam ◽  
Paul Aimé Noubissi ◽  
René Kamgang

Euphorbia scordifolia is used in Cameroon as galactagogue and in the treatment of gastrointestinal disorders. This work was undertaken to evaluate the acute and subchronic toxicities of ethanol/water extract of Euphorbia scordifolia (EWEs). Acute toxicity study was carried out by oral administration of 1, 2, 3, 4 and 5 g/kg body weight of EWEs to mice in the respective groups. Subchronic toxicity study was conducted by oral administration of the extract at daily doses of 50, 75 and 100 mg/kg body weight to another group of rats for 28 days, while rats in the control group received 10 mL/kg body weight of distilled water. Following the 28-day treatment, the rats were sacrificed for hematological, biochemical and histopathology studies. In the acute toxicity study, EWEs was found to be non-toxic at a dose of 5000 mg/kg body weight. The subchronic treatment with EWEs did not alter either the body weight gain or the food and water consumption. Biochemical analysis did not show any significant differences in any of the parameters examined in males or females. Hematological analysis showed a significant decrease (P<0.01) in white blood cells and red blood cells in males treated with 100 mg/kg bw and a significant (P<0.01) decrease in hemoglobin and hemoglobin hematocrit in all treated females. Necropsy and histopathological examination revealed some slight hepatic necrosis with the dose 100 mg/kg bw. It would be necessary to use the ethanol/water extract for short periods (<4 weeks). Thus, the plant, at least its ethanol/water extract, could be considered with a wide margin of safety for short-term oral use.


Author(s):  
O. L. Orobchenko ◽  
M. Ye. Romanko ◽  
M. O. Yaroshenko ◽  
I. O. Gerilovych ◽  
N. A. Zhukova ◽  
...  

The experiments were performed on 58 males of nonlinear white rats 3–4 months old and weighing 180–200 g and 64 females of nonlinear white mice 2.5–3 months old and weighing 18–22 g. In the main experiment on rats, six experimental groups were formed, the animals of which were injected intragastrically with the drug ‘MEGASTOP for dogs’ (by absolute weight) in doses of 1,000.0, 2,000.0, 3,000.0, 4,000.0, 5,000.0, and 6,000.0 mg/kg body weight; in the main experiment on mice, seven experimental groups were formed, the animals of which were administered the drug in doses of 100.0, 500.0, 1,000.0, 1,500.0, 2,000.0, 2,500.0, and 3,000.0 mg/kg body weight. Control rats and mice were injected with 2.0 cm3 and 0.2 cm3 of polyethylene glycol-400, respectively. Clinical symptoms of poisoning with the drug ‘MEGASTOP for dogs’ of white rats (at doses of 2,000.0–6,000.0 mg/kg body weight) and mice (at doses of 1,000.0–3,000.0 mg/kg body weight) were refusals of food and water, loss of coordination, sitting in one place, a dose-dependent increase in depression with subsequent complete depression, lack of response to external stimuli and death on the first or fourth day after administration. During autopsy in rats and mice that died as a result of poisoning with the drug ‘MEGASTOP for dogs’, we recorded pallor of the mucous membranes of the mouth, trachea, pharynx, and esophagus; increase in heart volume, atrial blood supply; pulmonary hyperemia; uncoagulated blood; increase in liver volume, dark cherry color, flabby consistency; catarrhal inflammation of the mucous membrane of the small intestine. According to the results of determining the parameters of acute toxicity of the drug ‘MEGASTOP for dogs’ in the case of a single intragastric injection, LD50 for male rats is 3,384.98 ± 444.94 mg/kg, and for female mice — 2,025.88 ± 279.46 mg/kg body weight, which allows to classify it to class IV by the toxicity — low-toxic substances (LD50 — 501–5,000 mg/kg) and by the degree of danger to class III— moderately dangerous substances (LD50 — 151–5,000 mg/kg)


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.


1996 ◽  
Vol 14 (4) ◽  
pp. 1048-1054 ◽  
Author(s):  
H Wada ◽  
S Hitomi ◽  
T Teramatsu

PURPOSE We performed a study to determine whether postoperative mild chemotherapy to maintain the patient's quality of life (QOL) and immunoactivity could also prolong survival. SUBJECT AND METHODS From December 1985 to July 1988, 323 patients with completely resected primary non-small-cell lung cancer (stage I to III) were enrolled. The subjects were randomized into three treatment groups, as follows: cisplatin (CDDP) 50 mg/m2 body surface, vindesine (VDS) 2 to 3 mg/kg body weight for three courses, and 1-year oral administration of tegafur (FT) plus uracil (UFT) 400 mg/kg body weight (CVUft group, 115 patients); 1-year oral administration of UFT 400 mg/kg body weight (Uft group, 108 patients); or surgical treatment only (control group, 100 patients). RESULTS The overall 5-year survival rates were 60.6% for the CVUft group and 64.1% for the Uft group versus 49.0% for the control group. The results of statistical testing were P = .053 (log-rank test) and P = .044 (generalized Wilcoxon test) among the three groups, P = .083 (log-rank) and P = .074 (Wilcoxon) between the CVUft and the control groups, and P = .022 (log-rank) and P = .019 (Wilcoxon) between the Uft and the control groups, which indicates higher survival rates in the CVUft and the Uft groups compared with the control group. A multivariate statistical analysis on prognostic factors using Cox's proportional hazards model was performed with the following results: P = .037, hazards ratio = 0.64 with a 95% confidence interval (CI) of 0.42 to 0.97 (control v CVUft group); and P = .009, hazards ratio = 0.55 with a 95% CI of 0.36 to 0.86 (control v Uft group). CONCLUSION Significantly favorable results were obtained in the CVUft and Uft groups compared with surgery alone. These data showed significant prognostic advantages in the postoperative adjuvant chemotherapy groups.


2015 ◽  
Vol 61 (1) ◽  
pp. 92-98
Author(s):  
O.N. Tananova ◽  
E.A. Arianova ◽  
I.V. Gmoshinskii ◽  
I.Yu. Toropygin ◽  
E.V. Khryapova ◽  
...  

The effect of daily intragastric administration of an aqueous dispersion of silicon nanoparticles (NPs) (the dose range from 1.0 mg/kg to 100 mg/kg body weight for 28 days) to rats on the proteomic profile of liver microsomes has been investigated by 2D-electrophoresis followed by subsequent mass spectrometry identification. The liver microsomal fraction was isolated by differential centrifugation and its protein composition was analyzed by 2D-polyacrylamide gel electrophoresis. Identification of protein spots was carried out using MALDI-TOF mass spectrometric analysis. The mass spectrometry analysis revealed the protein GRP78 (78 kD glucose-regulated protein precursor), belonging to the family of heat shock proteins. This protein present in animals of the control group was not detected in NP-treated rats of group 2 (1 mg/kg body weight/day) and group 3 (10 mg/kg body weight/day). This protein predominantly localized in the liver cell endoplasmic reticulum and plasma membrane has the chaperone biological activity. Possible mechanisms of the effects of engineered nanoparticles on biosynthetic processes in the body are discussed.


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