scholarly journals Toxicological Characteristics Of N-Deacetyllappaconitine Under Chronic Administration In White Rats

2021 ◽  
Vol 03 (03) ◽  
pp. 34-41
Author(s):  
Lola Tishaevna Zakhidova ◽  

In chronic experiments in laboratory animals, studied toxicological perspective new antiarrhythmic effect of N-deacetyllappaconitine for the treatment of arrhythmic states, an original herbal preparation based on Aconitum leucostonum, Ac.Septentrionale was created. During 2,5 months of intragastric administration in animals exposed to all doses of N-deacetyllappaconitine, no deviations in the parameters of the functioning of the nervous system were found, therefore, this value is the lowest effective (threshold) dose in a chronic experiment.

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):  
E. K. Rakhmatullin ◽  
O. D. Sklyarov

The article presents the results of a study of the "Bisolbi" drug toxicity (powder of light ash color, poorly soluble in water). When it is mixed with water it forms a suspension of particles that settle rapidly. Values of acute drug toxicity were determined on rats. We studied groups of six animals of the same sex, as well as similar control ones. The "Bisolbi" drug was injected to white rats intragastrically, males weighing 310 ... 320 g in doses of 2500 and 2740 mg / kg. Each dose was used in six animals; distilled water (3 ml) was used for the controls. The LD50 was calculated by the probit analysis method proposed by Litchfield and Wilcoxon modified by Z. Roth. When administered orally, an atraumatic metal probe was immersed in the stomach. Within 14 days monitored the overall health status and behavior of animals, the manifestation or absence of symptoms of intoxication; noted the features of feed and water ingestion, assessed the condition of the coat, physiological functions. Then groups of experimental rats were euthanized and pathomorphologically examined. We studied the effect of "Bisolbi" with repeated introduction and on not purebred dogs. Two groups of 3-4 years of age were completed with an average initial body weight of 13.63 ... 15.11 kg. Before use, the additive was thoroughly mixed with feed. The drug was injected during 31 days at a dose of 0.5 g / kg. Dogs of the control group (three) were fed wheat flour. After 15 and 31 days in laboratory animals in order to characterize the general condition in the blood, the amount of protein, urea, glucose, creatinine, cholesterol were determined. Based on studies it was found that the drug daily application by animals, is low toxic and safe, does not provoke the development of pathological reactions. According to the Hodge and Sterner classification "Bisolbi" can be attributed to the 6th class of toxicity - relatively harmless. Accordingto GOST 12.1.007-76 LD50 of the drug is more than 151 mg / kg, but less than 5000 mg / kg it is the 3rd hazard class (moderately hazardous).


Author(s):  
B.A. Katsnelson ◽  
M.P. Sutunkova ◽  
L.I. Privalova ◽  
S.N. Solovjeva ◽  
V.B. Gurvich ◽  
...  

The article presents in an experiment obtained principal results based on repeated low-level inhalation exposures of laboratory animals (white rats, outbred) to nickel oxide nanoparticles with a diameter of (23 ± 5) nm, 4 hours a day, 5 times a week for up to 10 months in a «nose only» installation. It was shown that non-specific body reactions to the action of NiO NPs include: diverse manifestations of systemic toxicity with a particularly pronounced influence on liver and kidney function, redox balance, damage to some areas of brain tissue, associated with proven movement of the nanoparticles themselves from the nasal mucosa along the olfactory tract; some cytological signs of probable development for allergic syndrome; paradoxically low severity of pulmonary pathology by pneumoconiotic type explained by a small chronic delay of nanoparticles in the lungs; the genotoxic effect of the organismal level, even at those low levels of chronic exposure, at which systemic toxicity is rather poorly. Along with that, NiO NPs also induce phase-stimulation of erythropoiesis, which is relatively specific for the toxic nickel effects.


Author(s):  
Elizabeth Hampson

Organizational and activational effects of sex steroids were first discovered in laboratory animals, but these concepts extend to hormonal actions in the human central nervous system. This chapter begins with a brief overview of how sex steroids act in the brain and how the organizational-activational hypothesis originated in the field of endocrinology. It then reviews common methods used to study these effects in humans. Interestingly, certain cognitive functions appear to be subject to modification by sex steroids, and these endocrine influences may help explain the sex differences often seen in these functions. The chapter considers spatial cognition as a representative example because the spatial family of functions has received the most study by researchers interested in the biological roots of sex differences in cognition. The chapter reviews evidence that supports an influence of both androgens and estrogens on spatial functions, and concludes with a glimpse of where the field is headed.


2010 ◽  
Vol 298 (5) ◽  
pp. E1088-E1096 ◽  
Author(s):  
Diego Pérez-Tilve ◽  
Lucas González-Matías ◽  
Benedikt A. Aulinger ◽  
Mayte Alvarez-Crespo ◽  
Manuel Gil-Lozano ◽  
...  

Exendin-4 (Ex-4), an agonist of the glucagon-like peptide-1 receptor (GLP-1R), shares many of the actions of GLP-1 on pancreatic islets, the central nervous system (CNS), and the gastrointestinal tract that mediates glucose homeostasis and food intake. Because Ex-4 has a much longer plasma half-life than GLP-1, it is an effective drug for reducing blood glucose levels in patients with type 2 diabetes mellitus (T2DM). Here, we report that acute administration of Ex-4, in relatively high doses, into either the peripheral circulation or the CNS, paradoxically increased blood glucose levels in rats. This effect was independent of the insulinotropic and hypothalamic-pituitary-adrenal activating actions of Ex-4 and could be blocked by a GLP-1R antagonist. Comparable doses of GLP-1 did not induce hyperglycemia, even when protected from rapid metabolism by a dipeptidyl peptidase IV inhibitor. Acute hyperglycemia induced by Ex-4 was blocked by hexamethonium, guanethidine, and adrenal medullectomy, indicating that this effect was mediated by sympathetic nervous system (SNS) activation. The potency of Ex-4 to elevate blood glucose waned with chronic administration such that after 6 days the familiar actions of Ex-4 to improve glucose tolerance were evident. These findings indicate that, in rats, high doses of Ex-4 activate a SNS response that can overcome the expected benefits of this peptide on glucose metabolism and actually raise blood glucose. These results have important implications for the design and interpretation of studies using Ex-4 in rats. Moreover, since there are many similarities in the response of the GLP-1R system across mammalian species, it is important to consider whether there is acute activation of the SNS by Ex-4 in humans.


2021 ◽  
Vol 22 (1) ◽  
pp. 14-19
Author(s):  
L. F. Almakaeva ◽  
◽  
G. A. Bajburina ◽  
F. H. Kamilov ◽  
D. Yu. Grebnev ◽  
...  

Aim. Study of the hormonal status and the level of pro-inflammatory cytokines in the blood plasma in experimental hypothyroidism and the effect of the organoiodine complex with rebaudioside A. Materials and methods. Endemic thyroid dysfunction was modeled in sexually mature male white rats by daily intragastric administration of thiamazole for 21 days at a dose of 25 mg / kg. In the blood serum, the content of thyrotropin, total and free thyroxine, total triiodothyronine, testosterone, luteinizing, follicle-stimulating and parathyroid hormones, corticosterone, interleukins-1-beta and -6, tumor necrosis factor-alpha was studied. The animals were divided into four groups of 10 each: control, experimental, comparison and main. Results. The development of hypothyroidism was characterized by an increase in the content of thyroid-stimulating, luteinizing, follicle-stimulating and parathyroid hormones, as well as pro-inflammatory cytokines. At the same time, testosterone levels decreased, while corticosterone levels were within physiological fluctuations. Conclusion. The use within 30 days of the recovery period after the development of hypothyroidism of the iodosaccharide complex based on steviol glycoside rebaudioside A used in the food industry daily at a dose of 25 mg / kg of rat weight led to the normalization of the content of the studied hormones and cytokines in the blood plasma, characterizing the effectiveness of the new organoiodine product.


Author(s):  
Anna L. Yasenyavskaya ◽  
Alexandra A. Tsibizova ◽  
Lyudmila A. Andreeva ◽  
Nikolay F. Myasoedov ◽  
Olga A. Bashkina ◽  
...  

Objective. To investigate the effect of glyprolines on the levels of initiating and effector caspases in the serum of white rats under "social" stress. Materials and methods. The study was conducted on 90 white male rats of 6 months of age. All manipulations with animals were carried out in accordance with international and domestic requirements for working with laboratory animals. When modeling "social" stress, groups of animals with aggressive and submissive behavior were formed. Laboratory animals, taking into account the types of behavior, were divided into groups (n=10): a group of intact males (control); a group of animals exposed to" social " stress for 20 days (stress); groups of individuals who received intraperitoneal Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), Pro-Gly-Pro, Pro-Gly-Pro-Leu at doses of 100 mcg/kg / day from the 1st day of stress exposure within a 20- day course. The effect of neuropeptides on the activity of apoptosis processes was evaluated by determining the level of initiating and effector caspases (caspase-8 and caspase-3) (ELISA Kit for Caspase-8 and ELISA Kit for Caspase-3; USA) in the blood serum of white rats by enzyme immunoassay. Results. According to the results of the study, it was found that under conditions of "social" stress, an increase in apoptotic processes was observed, accompanied by an increase in the level of caspase-3 and caspase-8 in the blood serum of white rats. The introduction of the studied compounds against the background of stress contributed to a decrease in the level of the studied indicators, which is most likely due to the presence of antiapoptotic action in glyprolins due to inhibition of the caspase-dependent cascade of apoptosis reactions, as a result of which the destruction of cellular structures occurs by hydrolysis of nuclear lamina, cleavage of adhesive proteins, destruction of the cytoskeleton. Conclusion. Thus, the conducted study established the presence of Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selank), Pro-Gly-Pro and Pro-Gly-Pro-Leu under conditions of stress-induced antiapoptotic activity due to inhibition of the caspase-dependent cascade of apoptosis reactions.


2021 ◽  
Vol 29 (5) ◽  
pp. 25-33
Author(s):  
Vadzim Michailovich Vasilkevich ◽  
Ruslan Valerievich Bogdanov ◽  
Ksenia Sergeevna Gilevskaya ◽  
Victoria Igorevna Kulikouskaya

Introduction. Nanocomposites synthesized by the “green chemistry” method do not contain toxic chemicals (reducing agents and organic solvents) as carriers and/or stabilizing shells. One of the representatives of this group of materials are nanocomposites based on silver, which are increasingly used in medical practice, veterinary medicine, and in some other fields. Material and methods. The nanocomposite is Ag0 nanoparticles coated with a highly methoxylated pectin shell. The concentration of Ag0 nanoparticles in the hydrosol of the pectin-Ag nanocomposite is 1.65 mmol/l, and the pectin content is 7.5 mg/ml. The size of the synthesized pectin-Ag nanocomposite is ~20-30 nm, more than 90% of the particles have a diameter of less than 20 nm, the value of the ξ-potential is 45.3 ± 0.7 mV. Toxicological studies were carried out on outbred rats. The main goal of the research was to study the toxic effects of the pectin-Ag nanocomposite in a subchronic experiment (90 days). At the end of the experiment, a complex of behavioral and clinical and laboratory parameters was determined, which made it possible to assess the biological effect of the nanocomposite on animals. The research results were statistically processed. Results. With subchronic intragastric administration of the pectin-Ag nanocomposite to laboratory animals (rats) for 3 months at doses of 50, 500, and 5000 mg/kg, it was found that the nanocomposite exhibits a dose-dependent general toxic effect with critical target organs - the liver and spleen and the main biochemical markers of toxicity effect - aminotransferase, alkaline phosphatase and lactate dehydrogenase. Conclusion. Experimental studies have made it possible to substantiate the threshold doses of the hydrosol of the pectin-Ag nanocomposite for the intragastric route of intake.


1956 ◽  
Vol 34 (1) ◽  
pp. 689-712 ◽  
Author(s):  
C. G. Drake ◽  
J. J. Seguin ◽  
G. W. Stavraky

The effects of removal of one motor cortex, a frontal lobe, or a complete cerebral hemisphere on the action of various convulsant agents were studied in chronic cats and in spinal preparations. In both sets of experiments, previously decentralized neurons responded to smaller quantities of convulsant drugs than did the intact ones, and pentylenetetrazol, camphor, and picrotoxin, as well as strychnine and acetylcholine, evoked greater and more prolonged responses from these neurons when sufficient time was allowed for sensitization due to partial isolation to take place (in the majority of experiments two to eight months).This was ascertained in myographic recordings and in studies of the electrical activity of the anterior horn cells in high spinal cats and white rats, as well as in photographic and statistical analyses of convulsions induced in chronic animals. The latter study revealed that the convulsions were asymmetrical in the operated cats, the muscular contractions being exaggerated and prolonged contralaterally to the cerebral ablation. The median convulsant dose (CD50) of pentylenetetrazol for the control cats was 7.8 mgm./kgm. (95% confidence limits 7.4–8.1) while that for the operated group was 6.8 mgm./kgm. (95% confidence limits 6.3–7.2). The latent period following the injection of pentylenetetrazol was significantly shorter for the operated group than for the control one, and the convulsions lasted longer in the operated cats than in intact animals. The longer duration of convulsions in the operated group depended on a significantly longer tonic and terminal clonic phase of the convulsion. Two patterns of convulsions could be elicited—a clonic and a more severe clonic–tonic–clonic (CTC) one. In the control group clonic convulsions were more frequent at low dosages of pentylenetetrazol while CTC convulsions pre-dominated at high dosages. In the operated group CTC convulsions were prevalent throughout the range of doses used and occurred in a greater percentage of animals than in the control group. Chemically induced convulsions play a prominent part in the study of epilepsy and in the treatment of some mental derangements, and it is felt that this investigation may contribute to the understanding of the mechanism of action of convulsant agents on the nervous system in which abnormal conditions prevail.


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