scholarly journals EFFECT OF AP-1 TRANSCRIPTION FACTOR INHIBITOR ON STRUCTURAL, METABOLIC AND BIOMECHANICAL CHANGES IN BONE TISSUE DURING COMBINED EXCESSIVE INTAKE OF SODIUM FLUORIDE AND SODIUM NITRATE

2019 ◽  
Vol 19 (2) ◽  
pp. 123-128
Author(s):  
I.O. Kovalova ◽  
V.O. Kostenko
Keyword(s):  
Transcription Factor ◽  
Body Weight ◽  
Bone Tissue ◽  
Sodium Fluoride ◽  
Sodium Nitrate ◽  
Total Activity ◽  
Experimental Conditions ◽  
White Rats ◽  
Factor Inhibitor ◽  
Excessive Intake

This article highlights the effect produced by the inhibitor of the AP-1 transcription factor activation on the mechanisms of structural, metabolic and biomechanical disorders in the femoral bones and vertebrae during combined excessive intake of sodium fluoride and sodium nitrate. The experiment was conducted on 30 white rats divided into 4 groups: the 1st included the intact animals, the 2nd group involved the rats subjected to the co- administration of sodium fluoride (10 mg / kg body weight) and sodium nitrate (500 mg / kg body weight) for 30 days, the 3rd group included the animals, which starting from the 15th day of intoxication, were injected SR 11302 ((E, E, Z, E) -3-Methyl-7- (4-methylphenyl) - 9- (2,6,6-trimethyl-1-cyclohexen-1-yl) -2,4,6,8-nonatetraenoic acid), an inhibitor of AP-1 activation in a dose of 1 mg / kg intraperitoneally 3 times a week. It has been revealed that the SR 11302 administration restores the mechanism of NO autoregulation in the femoral bones during the sodium fluoride and sodium nitrate co- administration, reducing the total activity of NO synthase and activity of its inducible isoform under a reciprocal increase in total arginase activity, and suppresses the peroxynitrite production. This is accompanied by a decrease in the activity of enzymes, which are known as markers of bone resorption (acid phosphatase and its bone isoform) and restriction of the depolymerization of collagen, proteoglycans and sialoglycoproteins of the connective (bone) tissue in the femurs and vertebrae. Moreover, the introduction of SR 11302 under the experimental conditions is accompanied by an increase in the density and mineral saturation of the femurs and vertebrae, and an improvement in the biomechanical characteristics of the femurs (their strength and elasticity).

scholarly journals MORPHOFUNCTIONAL STATE OF HEPATOCYTES UNDER THE EXPOSURE TO SODIUM FLUORIDE

2020 ◽  
Vol 20 (3) ◽  
pp. 196-199
Author(s):  
I.L. Kolisnyk ◽  
I.Yu. Bagmut
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Aqueous Solutions ◽  
Sodium Fluoride ◽  
Redox Reactions ◽  
Ultrastructural Organization ◽  
Partial Reduction ◽  
White Rats ◽  
Subcellular Level

The article provides the data on the morphofunctional state of hepatocytes in the liver of white rats under the subtoxic action of sodium fluoride. Mature rats of the Wistar population (N = 17), weighing 180-210 g, were intragastrically injected with aqueous solutions of sodium fluoride in a dose of 1/10 LD50 at the ratio of 20 mg / kg of animal body weight daily. The subacute experiment lasted 60 days. Studying hepatocytes in the rat liver and assessing their morphological rearrangement at the subcellular level of organization was carried out by electron microscopy. The study of ultrastructural organization of the liver under the influence of sodium fluoride revealed changes in the submicroscopic architecture characteristic of the development of dystrophic processes. Prolonged intoxication with sodium fluoride caused a number of changes in the liver ultrastructurer, manifested by the development of intracellular edema in hepatocytes, swelling of mitochondria, changes in the density of their matrix, partial reduction and loss of cristae, vacuolization and expansion of the cisterns of the granular endoplasmic reticulum, an increase in the number of primary lysosomes, redistribution chromatin of the nucleus and a decrease in the number of ribosomes and glycogen granules. These changes indicate a disruption of bioenergetics of hepatocytes associated with the mitochondrial apparatus and the development of hypoxic processes, which lead to a decrease in the activity of redox reactions occurring at the level of intracellular membranes and organelles.

scholarly journals EFFECT OF TRANSCRIPTION FACTOR KAPPA B INHIBITORS ON METABOLIC AND STRUCTURAL DISORDERS IN BONE TISSUE UNDER COMBINED EXCESSIVE INTAKE OF FLUORIDE AND SODIUM NITRATE

2019 ◽  
Vol 19 (1) ◽  
pp. 65-70
Author(s):  
I.O. Kovalova ◽  
V.O. Kostenko
Keyword(s):  
Body Weight ◽  
Bone Mass ◽  
Sodium Nitrate ◽  
Nitrogen Monoxide ◽  
Total Activity ◽  
No Synthase ◽  
Water Soluble ◽  
Arginase Activity ◽  
Soluble Form ◽  
Structural Disorders

This experiment carried on 40 white Wistar rats aimed at studying the effect produced by inhibitors of the nuclear transcriptional factor kappa B (NF-κB) activation on the mechanisms of metabolic and structural disorders in the femoral bones and vertebrae under combined surplus fluoride and sodium nitrate intake. It has been found out that co-administration of sodium fluoride (10 mg/kg body weight) and sodium nitrate (500 mg/kg of body weight) for 30 days disrupts the autoregulation mechanism of nitrogen monoxide (NO) level in the femoral bones of the test rats that is manifested by an increase in the activity of total NO synthase and its inducible isoform against the background of a decrease in the total arginase activity and the activity of the constitutive NO synthase isoenzymes. Under these conditions, there has been observed the growth in the concentration of free hydroxyproline, N-acetylneuraminic and hexuronic acids in the femoral bones and vertebrae that is indicative of depolymerization of collagen, sialoglycoproteins and proteoglycans, decrease in bone mass, their density, mineral saturation, strength (the Simon index elevated). Inhibitors of NF-κB activation (ammonium pyrolidine dithiocarbamate and a water-soluble form of quercetin) restore the autoregulation mechanism of the NO level in the rats’ femoral bones that is accompanied by a decrease in the total activity of NO synthase, the activity of its inducible isoform, an increase in the total arginase activity and by limited peroxinitrite formation. Ammonium pyrolidine dithiocarbamate and a water-soluble form of quercetin have been shown to result in lowering in the content of free hydroxyproline, N-acetylneuraminic and hexuronic acids in bones that confirms their effectiveness as a means for correcting depolymerization of collagen, sialoglycoproteins and proteoglycans. There has been found their property to promote the growth of bone mass and density of the femurs and vertebrae.

Резекция печени изменяет механизмы выведения аммиака почками крыс с хроническим тетрахлорметановым гепатитом

2018 ◽  
pp. 72-79
Author(s):  
П.Н. Савилов ◽  
Д.В. Молчанов
Keyword(s):  
Body Weight ◽  
Toxic Hepatitis ◽  
Ammonia Excretion ◽  
Left Lobe ◽  
Free Form ◽  
Sham Operation ◽  
White Rats ◽  
Urea Reabsorption ◽  
Ambiguous Effect ◽  
Collecting Tubules

Цель исследования - изучение влияния резекции печени (РП) на аммиакэкскретирующую функцию почек при хроническом тетрахлорметановом гепатите. Методика. Опыты выполнены на 265 беспородных белых крысах (самках) массой 180-220 г. Хронический гепатит воспроизводили подкожным введением 50% раствора тетрахлорметана (CCl) на оливковом масле (0,1 мл/100 г массы тела, через сутки, c двумя двухнедельными перерывами между 6, 7 и 13-14 инъекциями). На 65-е сут. (последние) введения тетрахлорметана, удаляли часть левой доли печени (15-20% массы органа). На 3-и, 7-е и 14-е сут. после РП или лапаротомии («ложнооперированные» животные) в почках, артериальной и венозной крови, моче исследовали содержание аммиака, глутамина и мочевины. Результаты. Прогрессирование эндогенной аммиачной интоксикации после РП на фоне тетрахлорметанового гепатита сопровождается повышенной экскрецией аммиака почками. Однако это не устраняет артериальную гипераммониемию и не предотвращает накопление почками аммиака. Инкреция глютамина из почек в кровоток прекращается. К 14-м сут. послеоперационного периода возрастает потребление глютамина из артериальной крови, что приводит к его накоплению в почках. Стимулируя выведение мочевины из организма с мочой, РП одновременно активирует её образование в почках, с дальнейшим поступлением как в кровоток, так и в мочу. В зависимости от сроков послеоперационного периода это сопровождается изменением скорости реабсорбции мочевины в почках. Заключение. Полученные результаты свидетельствуют, что при РП на фоне тетрахлорметанового гепатита почки не предотвращают прогрессирование эндогенной аммиачной интоксикации, патологическое накопление аммиака и глутамина её клетками, но сохраняют способность принимать участие в регуляции повышенного содержания мочевины в артериальной крови. Mechanical (resection) or toxic (hepatitis) liver damage alone has an ambiguous effect on renal ammonia excretion during development of endogenous ammonia intoxication. The aim. The study investigated the effect of liver resection (LR) on renal ammonia excretion in chronic tetrachlorocarbon (CCl)-induced hepatitis. Methods. Experiments were conducted on 240 mongrel white rats (females) weighing 180-220 g. Chronic hepatitis was induced by subcutaneous injection of 50% solution of carbon tetrachloride (CCl) in olive oil (0.1 ml/100g body weight per day with two two-week breaks between injections 6-7 and 13-14). LR with removal of a part of the left lobe (15-20% of body weight) was performed on the 65th (last) day of CCl injections. The animals were examined on the 3rd, 7th and 14th day after LR or laparotomy (sham operation). Contents of ammonia (AM), glutamine (GN), and urea were measured in the kidney, arterial (AB) and venous ( v.renlis ) blood, and urine. Results. Progression of endogenous ammonia intoxication after LR associated with CCl-induced hepatitis and increased renal excretion of Am involves three mechanisms: 1) excretion of Am that is delivered to kidneys in the free form with AB; 2) stimulation of renal tubule secretion of Am that had formed in kidneys by deamidation of «arterial» Gn; and 3) contrary to rules, partial reabsorption of Am from collecting tubules into the blood. However, this does not eliminate arterial hyperammonemia or prevent accumulation of Am in kidneys. The stimulatory effect of LR in CCl-induced hepatitis on Gn incretion from kidneys to the circulation stops by the 14 day after surgery, and the accompanying increased consumption of Gn from AВ results in Gn accumulation in kidneys. LR stimulates urea excretion with urine and simultaneously activates kidney formation of urea, which further enters the bloodstream and urine. Depending on the postoperative period this is associated with changes in the rate of urea reabsorption in kidneys. Conclusions. In RP associated with CCl-induced hepatitis, kidneys cannot prevent progression of endogenous ammonia intoxication and pathological accumulation of ammonia and glutamine in kidney cells but retain the ability to participate in the regulation of the increased urea level in AB.

The Arabidopsis NIM1 Protein Shows Homology to the Mammalian Transcription Factor Inhibitor IkB

1997 ◽  
Vol 9 (3) ◽  
pp. 425 ◽  
Author(s):  
John Ryals ◽  
Kris Weymann ◽  
Kay Lawton ◽  
Leslie Friedrich ◽  
Daniel Ellis ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Factor Inhibitor

THE INFLUENCE OF SORPTION-DETOXIFYING MEANS ON CUMULATION OF 90SR IN BONE TISSUE OF WHITE RATES WITH COMBINED INTAKE OF 137CS, CD AND PB

2018 ◽  
Vol 1 (3) ◽  
pp. 129-133
Author(s):  
L. L. Zakharova ◽  
◽  
G. A. Zhorov ◽  
V. N. Obryvin ◽  
◽  
...  
Keyword(s):  
Bone Tissue ◽  
Chemical Nature ◽  
Mechanisms Of Action ◽  
The Body ◽  
Biologically Active ◽  
Laboratory Studies ◽  
Animal Body ◽  
White Rats ◽  
Combined Use ◽  
Active Substances

The article presents the results of laboratory studies of the effect of sorption-detoxifying means on the accumulation of 90Sr in the body of white rats. The efficiency of a number of selective and polyfunctional sorbents, detoxicants and other biologically active substances and the developed on their basis sorption-detoxifying complexes as means of efferent therapy and detoxification of the animal body at the combined intake of xenobiotics of radiation and chemical nature was evaluated. It was found that 90Sr cumulation in bones (at the level of 53,3–60,8%) was reduced to the greatest extent with the combined use of substances of different mechanisms of action and origin. The effectiveness of separate use of detoxifying drugs did not exceed 29,1%.

scholarly journals Determination of acute toxicity parameters of the drug ‘MEGASTOP for dogs’ on white rats and mice

2020 ◽  
Vol 6 (2) ◽  
pp. 20-26
Author(s):  
O. L. Orobchenko ◽  
M. Ye. Romanko ◽  
M. O. Yaroshenko ◽  
I. O. Gerilovych ◽  
N. A. Zhukova ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Clinical Symptoms ◽  
Liver Volume ◽  
Male Rats ◽  
Toxic Substances ◽  
Main Experiment ◽  
Polyethylene Glycol 400 ◽  
White Rats ◽  
Rats And Mice

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)

scholarly journals Toxicity assessment of a technical product of the triazole class

2020 ◽  
Vol 99 (11) ◽  
pp. 1276-1279
Author(s):  
Valery N. Rakitskii ◽  
Tatiana M. Epishina ◽  
Elena G. Chkhvirkiya
Keyword(s):  
Body Weight ◽  
The Body ◽  
Male Rats ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
High Biological Activity ◽  
Experimental Animals ◽  
Technical Product ◽  
White Rats ◽  
Toxicological Studies

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.

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
Keyword(s):  
Body Weight ◽  
Soft Tissues ◽  
Control Level ◽  
Subcutaneous Administration ◽  
The Body ◽  
Laboratory Animals ◽  
Veterinary Drug ◽  
Intragastric Administration ◽  
Toxicological Evaluation ◽  
White Rats

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.

scholarly journals The Clinical and Hematological changes in Rabbits exposed to Melia azedarach fruits under experimental conditions

2015 ◽  
Vol 1 (1) ◽  
pp. 12 ◽  
Author(s):  
AL- Zubaedi Raad Mahmood
Keyword(s):  
Body Weight ◽  
Body Temperature ◽  
Bleeding Time ◽  
Hematological Parameters ◽  
The Body ◽  
Melia Azedarach ◽  
Control Group ◽  
Clotting Time ◽  
Experimental Conditions ◽  
Hb Concentration

The study was conducted on 10 local breed rabbits, of 1-2 years age, of 1- 1.5 kg body weight. They were feed concentrated and green food, and left ad libitum for water, and kept in room of 20- 25 oC. The animals divided into two groups of 5 each. First as treated group received the plant in powder form mixed with the food at a dose rate of 5 g/ animal / day for three weeks , while the second left without exposure as a control group .The main dependent parameters in the study were , clinical parameters ( body temperature , heartbeat , respiratory rate, body weight , in addition to monitor any abnormal signs appear on the animals . While the main hematological parameters were included , RBC count , WBC count , Hb concentration,PCV percentage , Red cell indices , Bleeding time and Clotting time. The body temperature, respiratory rates, heart rate were increased .The body weight decreased .The bleeding time and clotting time were prolonged. The erythrocyte count, Hb concentration, and MCV values were decreased; PCV and MCHC did not showed any significant changes. The MCH increased. The total leucocytes count and the basophiles percentage did not showed any significant changes. The Heterophils and monocytes percentage increased .The lymphocytic and Eosinophil percentage were decreased during the study.

THE EFFECT OF COLD ACCLIMATION ON THE SIZE OF ORGANS AND TISSUES OF THE RAT, WITH SPECIAL REFERENCE TO MODES OF EXPRESSION OF RESULTS

1958 ◽  
Vol 36 (2) ◽  
pp. 209-216 ◽  
Author(s):  
O. Heroux ◽  
N. T. Gridgeman
Keyword(s):  
Experimental Data ◽  
Body Weight ◽  
Special Reference ◽  
Cold Acclimation ◽  
Muscle Mass ◽  
Cold Adaptation ◽  
Organ Weight ◽  
Organ Weights ◽  
White Rats ◽  
Body Weights

In experiments in which two groups of animals of different mean body weight are compared, individual organ weights of the animals can be expressed as absolute weights, as fractional weights, or as absolute weights statistically regressed onto constant body weights. The second, and commonest, mode of expression involves the assumption that the part is directly proportional to the whole, and this is shown to be unlikely for all organs except the muscle mass. Practical as well as theoretical justifications for the use of regressed weights (which utilize the actual slope of the line relating the organ weight to the whole) are given.The experimental data are from white rats kept for 4 weeks in a warm (30 °C.) or a cold (6 °C.) environment. It is shown that cold adaptation had no effect on brain, genitals, and lung weights, but that it reduced the growth of muscle, pelt, fat, skeleton, spleen, and thymus, and that it hypertrophied the liver, intestine, kidney, heart, and adrenals. Apparently cold acclimated rats are smaller than the controls mainly because they have a smaller muscle mass.

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