Acute oral and cutaneous toxicities of cyflunit- flock tested on laboratory animals

2016 ◽  
Vol 3 (1) ◽  
pp. 114-118
Author(s):  
Глухарева ◽  
E. Glukhareva

Objective of research: to determine the toxicological properties of the preparation Cyflunit- Flock under acute experimental conditions at oral and subcutaneous administration routes to laboratory animals. Materials and methods: White outbred mice and white outbred rats of both genders were used for testing. Each dose of the preparation was tested on groups of males and females to identify the eventual sex differences in drug-responsiveness.In experiment on mice, animals were divided into 5 groups of 10 animals each.The medicine was given orally at the doses of 4350, 8700, 13050, 17400 and 21750 mg a.i./kg. In experiment on rats, 4 experimental male and 4 female groups were formed (6 animals in each). The drug was given orally at the doses of 17400 and 21750, 26100 and 30450 mg a.i./kg. While studying the acute cutaneous toxicity, Cyflunit- Flock was applied at the doses 870, 1740, 4350 and 8700 mg a.i./kgin 4 experimental groups of male and 4 groups of female rats of 6 animals each. Observations of general health status, behavior of animals, intoxication symptoms and eventual death of animals were conducted within 14 days. Results and discussion: LD50 of Cyflunit-Flockat oral administration to mice of both genders was 12180 mg/kg,at oral administration tomale rats - 22475 mg/kg, to female rats - 23925mg/kg. At cutaneous use of the preparation in rats, LD50 was more than 8700 mg/kg. Accordingtothestandardhygienicclassification, the preparation belongs to the 4thhazard class (low-hazard substances).

Cephalalgia ◽  
2018 ◽  
Vol 39 (2) ◽  
pp. 209-218 ◽  
Author(s):  
William J Scotton ◽  
Hannah F Botfield ◽  
Connar SJ Westgate ◽  
James L Mitchell ◽  
Andreas Yiangou ◽  
...  

Background The management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering intracranial pressure in healthy rats. Methods We measured intracranial pressure in female rats before and after subcutaneous administration of acetazolamide, topiramate, furosemide, amiloride and octreotide at clinical doses (equivalent to a single human dose) and high doses (equivalent to a human daily dose). In addition, we measured intracranial pressure after oral administration of acetazolamide and topiramate. Results At clinical and high doses, subcutaneous administration of topiramate lowered intracranial pressure by 32% ( p = 0.0009) and 21% ( p = 0.015) respectively. There was no significant reduction in intracranial pressure noted with acetazolamide, furosemide, amiloride or octreotide at any dose. Oral administration of topiramate significantly lowered intracranial pressure by 22% ( p = 0.018), compared to 5% reduction with acetazolamide ( p = >0.999). Conclusion Our in vivo studies demonstrated that both subcutaneous and oral administration of topiramate significantly lowers intracranial pressure. Other drugs tested, including acetazolamide, did not significantly reduce intracranial pressure. Future clinical trials evaluating the efficacy and side effects of topiramate in idiopathic intracranial hypertension patients would be of interest.


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 %”.


1961 ◽  
Vol 201 (4) ◽  
pp. 740-742 ◽  
Author(s):  
K. S. Kim

Urinary histamine output has been studied under various experimental conditions in rats. Orchidectomy increased the output of free histamine in rats of the Sprague-Dawley strain but not in rats of the Wistar strain. Subcutaneous administration of testosterone propionate (1 mg/rat) suppressed the output of free histamine in ovariectomized rats but not in normal females, which showed the effect only after repeated administration of this hormone. When exogenous histamine (100 µg) was administered at a constant rate over a 4-hr period, only a minute quantity of administered histamine appeared as free histamine in the urine of male rats. In contrast, 23% of administered histamine appeared as free histamine in the urine of female rats. When repeatedly treated with testosterone, female rats eliminated exogenous histamine more like males. The close relationship between testosterone and histamine metabolism in rats is thus clearly demonstrated.


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.


2020 ◽  
Vol 13 (9) ◽  
pp. 231
Author(s):  
Seung-Hyun Jeong ◽  
Ji-Hun Jang ◽  
Yong-Bok Lee

Topotecan is actively used in clinic, with its primary use being in treatment of various types of cancer. The approved administration routes are oral and intravenous. The purpose of this study was to investigate and identify pharmacokinetic profiles of different administration routes. We conducted pharmacokinetic studies on three different routes of administration in rats. Five rats in each group received a single dose of 4 mg/kg of topotecan hydrochloride intravenously, orally, or subcutaneously, and the concentrations of lactone and total forms of the drug in plasma, urine, and feces were quantified. Various pharmacokinetic parameters were compared statistically. Plasma concentrations of both the lactone and total forms at elimination phase following subcutaneous administration, were two times higher than was seen with oral administration and 10 times higher than with intravenous administration. Subcutaneous administration of topotecan showed pharmacokinetic profiles similar to sustained release. In addition, subcutaneous administration showed bioavailability from 88.05% (for lactone form) to 99.75% (for total form), and these values were four–five times greater than those of oral administration. The results of this non-clinical study will not only provide greater understanding of the in vivo pharmacokinetics of topotecan, but also be useful for development of additional formulations and/or administration routes.


1961 ◽  
Vol 38 (1) ◽  
pp. 50-58 ◽  
Author(s):  
N. E. Borglin ◽  
L. Bjersing

ABSTRACT Oestriol (oestra-1,3,5(10)-triene-3,16α,17β-triol) is a weakly oestrogenic substance which, however, in contrast to what was formerly believed, is of physiological significance. Its effect is localized largely to the uterine cervix and vagina. Clinical experience argues both for and against an effect on the pituitary gland. This investigation is concerned with the morphological changes in the pituitary gland and adrenal cortex of gonadectomized male and female rats after the injection of oestriol. It was found that oestriol has the same type of action on these glands as other oestrogens, but under the experimental conditions used, this effect proved much weaker than that produced by oestradiol (oestra-1,3,5(10)-triene-3,17β-diol).


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Murtala Akanji Abdullahi ◽  
Elijah Oladapo Oyinloye ◽  
Akinyinka Alabi ◽  
Aderonke Adeyinka Aderinola ◽  
Luqman Opeyemi Ogunjimi ◽  
...  

Abstract Objectives Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study. Methods Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods. Results The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible. Conclusions The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sabrina Passini ◽  
Laura Montoya ◽  
Martín Lupi ◽  
Paula Lorenzini ◽  
María Fabiana Landoni ◽  
...  

Clindamycin plasma and tissue disposition in cats under surgical conditions after a single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration at a dose rate of 10 mg/kg were studied. After intravenous, intramuscular and subcutaneous administration, peak plasma concentrations were 10.93±3.78 μg/mL (Cp(0)), 5.93±1.18 μg/mL (Cmax)) and 6.30±0.88 μg/mL (Cmax)), respectively. Eight hours after clindamycin IV, IM and SC administration plasma concentrations declined to 2.01±0.61 μg/mL, 2.96±0.43 μg/mL and 3.36±0.97 μg/mL, respectively. Sixty to 90 minutes after clindamycin administration, tissue concentrations ranged from a minimum in subcutaneous tissue of 4.90 μg/g (IV), 3.06 μg/g (IM) and, 3.13 μg/g (SC) to a maximum in uterus of 13.41 μg/g (IV), 14.07 μg/g (IM) and, 14.44 μg/g (SC). The lowest tissue/plasma concentration ratio for the three administration routes was observed in subcutaneous tissue, while the highest was observed at genital level (ovary for IV and IM and uterus for SC). Estimated efficacy predictor (AUC/MIC), considering MIC breakpoint for bacteria isolated from animals, indicates that clindamycin administered IV, IM or SC at the studied dose is appropriated for perioperative prophylactic protocols and that given with a dose interval of 12 hours would be effective for susceptible infection treatment in cats.


Author(s):  
V. V. Boyko ◽  
V. O. Prasol ◽  
D. V. Oklei ◽  
I. A. Taraban ◽  
P. O. Boldizhar

Based on the analysis of a large volume of the literature data concerning simulation of thrombotic conditions in laboratory animals under experimental conditions, the authors discuss various models of venous thrombosis. The method proposed by S. Wessler et al. (1959) is considered to be the simplest, most readily reproducible, and least invasive one. It consists of a combination of venous hyperemia and hypercoagulation induced by the administration of an activated coagulation factor.


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.


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