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1.
Environ Res ; 192: 110321, 2021 01.
Article in English | MEDLINE | ID: mdl-33075358

ABSTRACT

The genotoxic and antigenotoxic potential of BP-C2, a novel lignin-derived polyphenolic composition with ammonium molybdate, was investigated as a radioprotector/radiomitigator for civil applications and as a medical countermeasure for radiation emergencies. Using the alkaline comet assay and methyl methanesulfonate (MMS, 40 mg/kg) as the DNA-damaging agent, these effects of BP-C2 on liver, bone marrow cells and blood leukocytes in rats were studied. The DNA damage was estimated by the DNA content in the comet tail (TDNA, %) 1, 6 and 18 h post exposure to MMS. BP-C2 at doses of 20, 200 and 2000 mg/kg did not exert genotoxic activity in the tested tissues in rats. BP-C2 administered at doses of 20, 100 and 200 mg/kg 1 h before MMS significantly (p < 0.01) mitigated MMS-induced DNA damage, showing a strong genoprotective effect in the liver. In blood leukocytes and bone marrow samples of animals treated with BP-C2, the TDNA % was slightly higher than in the negative control (vehicle) but significantly lower than in the positive control (MMS). Thus, BP-C2 exerted a genoprotective effect against MMS-induced DNA damage to a greater extent towards liver cells, requiring further evaluation of this substance as a genoprotective agent.


Subject(s)
DNA Damage , Lignin , Animals , Comet Assay , Methyl Methanesulfonate/toxicity , Mutagens/toxicity , Protective Agents , Rats
2.
Adv Gerontol ; 33(4): 646-656, 2020.
Article in Russian | MEDLINE | ID: mdl-33342093

ABSTRACT

Radiation-protective and anti-aging properties are often combined. Combination of this properties is linked to the common mechanisms of action such as direct and indirect antioxidant activities, inhibition of free radicals formation, increase resistance to stress impacts at the cellular level, acceleration of DNA reparation, prevention of chronic diseases linked to abnormalities in regeneration processes, activation of immune inflammatory processes and carcinogenesis. Regulation of cell cycle and apoptosis can often be considered as an implementing driver of radiation-protective and anti-aging activities. On the one hand, against the background of stopping the cell cycle and blockade of apoptosis increases the time required to repair the defects of a DNA. Antiapoptotic effects enhances survival chances at the early stage after irradiation in a particular range of doses. On the other hand, activation of apoptosis of altered cells can be seen as one of the mechanisms to delay aging processes and prevention of isolated effects of exposure to ionizing radiation. Formation of radiation-induced and age-related alterations are characterized by multiple factors and a variety of manifestations. Nevertheless, similarity of individual links of the pathogenesis of disease related to radiation exposure and aging of the body is striking. It could be stated that radiation-protective property defines an increase in life expectancy by short-term exposure in sub-lethal and lethal doses. However anti-aging activities prevent the development of remote effects of ionizing radiation by prolonged low doses or fractionated exposure to radiation.


Subject(s)
Radiation-Protective Agents , Apoptosis , DNA Damage , Dose-Response Relationship, Radiation , Radiation, Ionizing , Radiation-Protective Agents/pharmacology
3.
Environ Res ; 191: 110049, 2020 12.
Article in English | MEDLINE | ID: mdl-32926891

ABSTRACT

Many natural substances exhibit anti-inflammatory activity and considerable potential in prophylaxis and treatment of allergies. Knowing exact molecular targets, which is required for developing these as medicinal products, is often challenging for multicomponent compositions. In the present study we examined novel polyphenolic substance, a water-soluble fraction of wood lignin (laboratory code BP-Cx-1). In our previous study, a number of polyphenolic components of BP-Cx-1 (flavonoids, sapogenins, phenanthrenes etc.) were identified as the major carriers of biological activity of BP-Cx drug family, and several molecular targets involved in cancer and/or inflammation signaling pathways were proposed based on the results of the in vitro and in silico screening studies. In the present study, half maximal inhibitory concentration (IC50) of BP-Cx-1 was established with a radioligand method and a range of IC50 values between 22.8 and 40.3 µg/ml were obtained for adenosine receptors A1, A2A and prostaglandin receptors EP2, IP (PGI2). IC50 for serotonin 5-HT1 and for glucocorticoid GR receptors were 3.0 µg/ml and 12.6 µg/ml, respectively, both being within the range of BP-Cx-1 concentrations achievable in in vivo models. Further, distribution of [3H] labelled BP-Cx-1 in NIH3T3 murine fibroblasts and MCF7/R carcinoma cells was studied with autoradiography. [3H]-BP-Cx-1 (visualized as silver grains produced by tritium beta particles) was mainly localized along the cell membrane, in the perinuclear region and in the nucleus, suggesting ability of BP-Cx-1 to enter cells and bind to membrane or cytosol receptors. In our experiment, we observed the effect of BP-Cx-1 on maturation of dendritic cells (DCs): downregulation of expression of the lipid-presentation molecule CD1a, co-stimulatory molecules CD80, CD83 and CD 40, decreased production of pro-inflammatory cytokines IL-4 and TNF-α and increased production of anti-inflammatory cytokine IL-10. It is hypothesized that [3H]-BP-Cx-1 detectable in the nucleus is part of the activated GR complex, known to be involved in regulation of transcription of genes responsible for the anti-inflammatory response. Based on IC50, cell distribution data and results of the experiment with DCs it is suggested that the in vivo effects of BP-Cx-1 are mediated via GR and 5-HT1 receptors thus promoting development of tolerogenic effector function in dendritic cells.


Subject(s)
Dendritic Cells , Lignin , Animals , Cytokines , Mice , NIH 3T3 Cells , Water
4.
Bull Exp Biol Med ; 165(2): 225-229, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29922996

ABSTRACT

We studied the dynamics of respiratory function in rats during intratracheal poisoning with diisopropyl fluorophosphate and pentylenetetrazole in doses corresponding to the LD50 in humans. The maximum of external respiration impairment was recorded in 30 min after poisoning. Administration of diazepam and atropine both separately and in combination during the development of the first signs of poisoning did not significantly affect the respiration parameters, but reduced the incidence of seizures and contributed to a decrease in the rate of animal death. Intratracheal administration of cholinolytic, ß2-adrenomimetic, or glutamate receptors antagonist promoted correction of the respiratory function. It was found that the maximum therapeutic effect in case of diisopropyl fluorophosphates poisoning was achieved after intratracheal administration of ipratropium bromide (0.086 mg/kg), salbutamol (0.086 mg/kg), and MK-801 (0.1 mg/kg), while in case of pentylenetetrazole poisoning, intratracheal administration of ipratropium bromide (0.086 mg/kg) was most effective.


Subject(s)
Bronchodilator Agents/administration & dosage , Isoflurophate/poisoning , Pentylenetetrazole/poisoning , Respiration Disorders/chemically induced , Respiration Disorders/drug therapy , Seizures/drug therapy , Administration, Inhalation , Albuterol/administration & dosage , Animals , Atropine/administration & dosage , Convulsants/poisoning , Diazepam/administration & dosage , Epilepsy/complications , Epilepsy/drug therapy , Epilepsy/pathology , Ipratropium/administration & dosage , Male , Rats , Respiration Disorders/complications , Respiration Disorders/pathology , Respiratory Mechanics/drug effects , Seizures/complications , Seizures/pathology
5.
Bull Exp Biol Med ; 165(1): 72-74, 2018 May.
Article in English | MEDLINE | ID: mdl-29797127

ABSTRACT

We studied association of Oprm1 gene polymorphisms with signs of N-(1-phenethyl-4-piperidyl)propionanilide intoxication in rats. It was found that the rate of intoxication in laboratory animals depends on genetic features. A polymorphic variant rs105312806 of Oprm1 gene can be a possible marker of animal sensitivity to opioid receptor agonists. This hypothesis was supported by differences in the rats of intoxication signs such as time to lateral posture and sleep duration in homozygous rats carrying different alleles. In rats with AA genotype, the time to lateral posture was shorter by 1.3 times and sleep duration was longer by 3.5 times than in carriers of GG genotype.


Subject(s)
Hypnotics and Sedatives/pharmacology , Polymorphism, Single Nucleotide/genetics , Receptors, Opioid, mu/genetics , Alleles , Animals , Genotype , Male , Rats , Receptors, Opioid, mu/antagonists & inhibitors , Receptors, Opioid, mu/metabolism , Sleep/drug effects
6.
Bull Exp Biol Med ; 164(6): 798-802, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29700681

ABSTRACT

We compared the efficiency of delivery of plasmid DNA (active ingredient concentration 1 mg/kg) that provides production of nerve growth factor (NGF) after intravenous administration to rats and after administration by hydroporation. The method of hydroporation ensured plasmid penetration into the liver tissue and lengthened the time of its detection in the organ. DNA concentration in 1 h after its introduction by hydroporation or intravenous route was 0.7 and 0.05 ng/mg tissue, respectively. The use of this transfection method ensured preservation of NGF DNA in the liver tissue at a level of 0.24 ng/mg of tissue 1 day after administration of the plasmid construct, while after intravenous administration, expression of the analyzed DNA was not detected in blood and liver samples. After hydroporation, the maximum of relative normalized expression of cDNA (270 rel. units) was observed after 4 h, and after 1 day, this parameter decreased to 35 rel. units. Introduction of plasmid DNA of NGF by hydroporation prevented the development of disorders of neuromuscular conduction in a rats model of toxic neuropathy induced by subacute administration of malathion in a dose of 0.5 LD50.


Subject(s)
Nerve Growth Factor/genetics , Neuroprotective Agents/metabolism , Peripheral Nervous System Diseases/therapy , Plasmids/metabolism , Transfection/methods , Animals , Cytomegalovirus/genetics , Cytomegalovirus/metabolism , Electromyography , Gene Expression , Injections, Intravenous , Insecticides/administration & dosage , Liver/metabolism , Liver/pathology , Malathion/administration & dosage , Male , Nerve Growth Factor/metabolism , Neural Conduction/drug effects , Neuroprotective Agents/pharmacology , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/genetics , Peripheral Nervous System Diseases/pathology , Plasmids/chemistry , Promoter Regions, Genetic , Rats
7.
Bull Exp Biol Med ; 163(6): 737-741, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29063329

ABSTRACT

We compared samples of microencapsulated naloxone prepared by using spray drying technique. 2-Hydroxypropyl-ß-cyclodextrin, sodium alginate, polycaprolactone, and carboxymethyl cellulose were used as the carriers. It was found that the combination of naloxone with sodium alginate was characterized by the highest naloxone content in the matrix and the lowest release rate (100% release time was 60 min). Using the model of respiratory disturbances caused by 10 ED50 fentanyl (anesthetic effect), we studied the effects of naloxone-sodium alginate complex on the dynamics of CO2 concentration in the expired air. It was shown that treatment with the developed microencapsulated naloxone after fentanyl injection allowed reducing the therapeutic dose of the antagonist by more than 2 times and eliminated the necessity of repeated injections.


Subject(s)
Drug Carriers , Fentanyl/poisoning , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Narcotics/poisoning , 2-Hydroxypropyl-beta-cyclodextrin/chemistry , Alginates/chemistry , Animals , Animals, Outbred Strains , Carboxymethylcellulose Sodium/chemistry , Drug Compounding/methods , Drug Liberation , Fentanyl/antagonists & inhibitors , Fentanyl/toxicity , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Kinetics , Male , Naloxone/metabolism , Narcotic Antagonists/metabolism , Narcotics/toxicity , Polyesters/chemistry , Rats , Respiration/drug effects
8.
Bull Exp Biol Med ; 162(2): 215-219, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27913936

ABSTRACT

The effects of analgesic substances trimeperidine and dexmedetomidine and their combinations in different proportions (0.75:0.25, 0.5:0.5, 0.25:0.75 of the medium effective doses of each substance) on respiratory function was studied in experiments on rats. Administration of substances in 1 ED50 by analgesic effect (corresponded to medium therapeutic dose of trimeperidine in humans) was characterized by significantly longer suppression of respiration over 90 min in comparison with combined treatment with these substances. Administration of the substances in a dose of 8 ED50 by analgesic effect (corresponded to daily therapeutic dose) over 60 min was followed by more than 3-fold reduction in respiration frequency and respiratory minute volume, more pronounced in animals receiving trimeperidine. Combined administration of these drugs in the specifi ed dose induced less pronounced suppression of respiration and combined administration of trimeperidine and dexmedetomidine in proportion of 0.75:0.25 signifi cantly reduced the period of restoration of respiratory parameters in comparison with animals receiving single substances.


Subject(s)
Analgesics, Non-Narcotic/pharmacology , Analgesics, Opioid/pharmacology , Dexmedetomidine/pharmacology , Promedol/pharmacology , Respiration/drug effects , Animals , Animals, Outbred Strains , Drug Administration Schedule , Drug Combinations , Drug Dosage Calculations , Male , Rats , Respiratory Function Tests
9.
Radiats Biol Radioecol ; 56(1): 64-72, 2016.
Article in Russian | MEDLINE | ID: mdl-27245006

ABSTRACT

Experiments on small (rats) and large (dogs) animals have shown that a sequential administration of Palonosetron and Phenotropil decreases the intensity of the main manifestations of the N-V-D stage of acute radiation syndrome. These data show the appropriateness of a combined administration of Palonosetron and Phenotropil to prevent a reduced work capacity in the individuals participating in elimination of the consequences of accidents associated with overexposure to radiation.


Subject(s)
Acute Radiation Syndrome/prevention & control , Isoquinolines/administration & dosage , Piracetam/analogs & derivatives , Quinuclidines/administration & dosage , Acute Radiation Syndrome/physiopathology , Animals , Dogs , Drug Combinations , Gamma Rays/adverse effects , Humans , Palonosetron , Piracetam/administration & dosage , Rats
10.
Voen Med Zh ; 337(12): 42-48, 2016 12.
Article in Russian | MEDLINE | ID: mdl-30592822

ABSTRACT

Present condition and perspective of development of self-care decontamination products. This work provides data describing the current state and perspectives of development of self-care decontamination products for neutralization and removal of poisonous and highly toxic biologic and radioactive agents from open human body surfaces and close- fitting cloth. The history of self-care decontamination products creation in Russia and foreign countries is represented. The detailed performance characteristics of the developed individual anti-gas kits IPP-3, IPP-51, IPP-8, IPP-10, IPP-11, which were accepted to the Army and the Navy supply in the 1920-1930s, during the Great Patriotic war, in post-war period and now, are given. The individual anti-gas kits RSDL, M291, M295 and MKI for government-issue equipment of North Atlantic nations' armies are described in detail. It was showed that the general limitation both of the native and foreign anti-gas kit models is the poor efficacy against exposure of vesicants from the group of blister warfare agents. The most perspective research guidelines in creation of new self-care decontamination products. are validated.


Subject(s)
Decontamination , Military Hygiene , Military Personnel , Self Care , Decontamination/instrumentation , Decontamination/methods , Humans , Military Hygiene/instrumentation , Military Hygiene/methods , Self Care/instrumentation , Self Care/methods
11.
Eksp Klin Farmakol ; 78(2): 34-8, 2015.
Article in Russian | MEDLINE | ID: mdl-25898546

ABSTRACT

A comparative study of the pharmacokinetics of levofloxacin and triazavirine as well as 2-methylthio-6-nitro-1,2,4-triazolo[5,1-ñ]-1,2,4-triazine-7(4Í)-ide (3S)-(-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-d,e]-1,4-benzoxazine-6-carboxylic acid (conjugate 2) obtained by conjugation of triazavirine and levofloxacin, representing a new class of pharmacological agents, was carried out in experiments on rats. It is established that conjugate 2 in comparison to individual levofloxacin and triazavirine has a higher relative bioavailability and lower rate of elimination, which can lead to improved effectiveness of therapy at reduced dose and frequency of drug administration.


Subject(s)
Anti-Infective Agents/pharmacokinetics , Azoles/pharmacokinetics , Carboxylic Acids/pharmacokinetics , Levofloxacin/pharmacokinetics , Triazines/pharmacokinetics , Animals , Anti-Infective Agents/blood , Anti-Infective Agents/chemistry , Azoles/blood , Azoles/chemistry , Biological Availability , Carboxylic Acids/blood , Carboxylic Acids/chemistry , Half-Life , Injections, Intramuscular , Levofloxacin/blood , Levofloxacin/chemistry , Male , Rats , Triazines/blood , Triazines/chemistry , Triazoles
12.
Voen Med Zh ; 335(5): 26-31, 2014 May.
Article in Russian | MEDLINE | ID: mdl-25286560

ABSTRACT

Authors consider causes of low efficiency of antidote therapy and ways of pharmacological tolerance management during medical treatment of organophosphate poisoning. One of the promising ways is a preventive antidote on the base of enzyme agents and allosteric modulators of a cholinesterase activity. Authors showed a expediency of a study of new acetylcholinesterase reactivators, its compositions and ways of drug delivery. Authors specified ways of searching for anticonvulsants from classes of quick-closing benzodiatines and NMDA-antagonists. Authors defined ways of improvement of methods of special antidotes delivery with targeted transport system. Authors made an assumption about the necessity of symptomatic treatment.


Subject(s)
Anticonvulsants/therapeutic use , Antidotes/therapeutic use , Chemical Warfare Agents/poisoning , Drug Delivery Systems/methods , Drug Resistance/drug effects , Organophosphate Poisoning/drug therapy , Acetylcholinesterase/metabolism , Humans , Organophosphate Poisoning/enzymology , Receptors, N-Methyl-D-Aspartate/agonists
13.
Eksp Klin Farmakol ; 77(4): 25-8, 2014.
Article in Russian | MEDLINE | ID: mdl-25076756

ABSTRACT

A comparative study of bemithyl pharmacokinetics was carried out upon its inhalation, intragastric and intravenous administration. The main drug metabolites were identified and the pharmacokinetic parameters were calculated. The obtained results suggest that the inhalation administration of bemithyl is a promising replacement for oral administration, which is related to high bioavailability of the drug and the absence of the effect of "first pass" through the liver.


Subject(s)
Anticonvulsants/pharmacology , Anticonvulsants/pharmacokinetics , Benzimidazoles/pharmacology , Benzimidazoles/pharmacokinetics , Liver/metabolism , Administration, Inhalation , Animals , Male , Rats
14.
Bull Exp Biol Med ; 155(3): 354-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-24137602

ABSTRACT

The efficiency of benzodiazepines on mouse model of anticholinesterase poisoning was shown. The protective effects of clonazepam and midazolam were observed at high (1 TD50, incoordination) and medium (0.3 TD50) doses and the effects of phenazepam and diazepam were found only at high doses. Midazolam produced the most pronounced protective effect: administration of this drug significantly increased the protective index of atropine+HI-6 combination during poisoning.


Subject(s)
Benzodiazepines/therapeutic use , Cholinesterase Inhibitors/poisoning , Animals , Atropine , Benzodiazepines/pharmacology , Cholinesterase Inhibitors/administration & dosage , Clonazepam/pharmacology , Diazepam/pharmacology , Dose-Response Relationship, Drug , Injections, Intramuscular , Male , Mice , Midazolam/pharmacology , Oximes , Pyridinium Compounds , Statistics, Nonparametric , Toxicity Tests
15.
Eksp Klin Farmakol ; 76(2): 3-5, 2013.
Article in Russian | MEDLINE | ID: mdl-23631274

ABSTRACT

The effect of memantine administration has been studied on the model of mice poisoning with an anticholinesterase compound. It is established that the memantine action is due to its influence on the cholinesterase activity in the brain, blood plasma, and erythrocytes in addition to its NMDA-blocking action. Memantine promotes oxime-induced erythrocyte enzyme reactivation on the model of mice poisoning with anticholinesterase compound (0.8 LD50).


Subject(s)
Anticonvulsants/pharmacology , Cholinesterase Reactivators/pharmacology , Memantine/pharmacology , Organophosphate Poisoning/drug therapy , Acetylcholinesterase/metabolism , Animals , Anticonvulsants/metabolism , Brain/drug effects , Brain/enzymology , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/poisoning , Cholinesterase Reactivators/metabolism , Erythrocytes/drug effects , Erythrocytes/enzymology , Isoflurophate/poisoning , Lethal Dose 50 , Male , Memantine/metabolism , Mice , N-Methylaspartate/antagonists & inhibitors , N-Methylaspartate/metabolism , Organophosphate Poisoning/blood , Oximes/metabolism
16.
Eksp Klin Farmakol ; 76(1): 3-6, 2013.
Article in Russian | MEDLINE | ID: mdl-23461007

ABSTRACT

Technological parameters for the effective encapsulation of n-(1-phenethyl-4-piperidyl)propionanilide in poly(lactid-co-glycolide) (PLG) nanoparticles have been determined. Depending on the ratio of drug fractions adsorbed on the particle surface and associated with the polymer matrix, n-(1-phenethyl-4-piperidyl)propionanilide (200 microg/kg, i/m) loaded PLG nanospheres accelerated time onset and increased duration of sleep in rats: by a factor of 1.6 - 2.0 for polymer associated drug fraction within 40 - 60% and by a factor of 2.2 - 2.6 for polymer associated drug fraction within 60 - 80%. A similar increase of sleep duration was observed when free n-(1-phenethyl-4-piperidyl)-propionanilide was administered at doses within 400 - 500 microg/kg.


Subject(s)
Drug Carriers/chemistry , Drug Compounding/methods , Hypnotics and Sedatives/pharmacology , Lactic Acid/chemistry , Nanoparticles/chemistry , Piperidines/pharmacology , Polyglycolic Acid/chemistry , Sleep/drug effects , Animals , Hypnotics and Sedatives/chemistry , Injections, Intramuscular , Male , Particle Size , Piperidines/chemistry , Poloxamer/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Rats
17.
Eksp Klin Farmakol ; 76(11): 19-22, 2013.
Article in Russian | MEDLINE | ID: mdl-24555228

ABSTRACT

The tolerance of five central muscarinic receptor antagonists has been studied in experimental animals. According to the effect on orientation-exploratory reaction, drugs were arranged in the following order of increasing toxicity: procyclidine < trihexiphenidyl < benactizine < atropine < scopolamine. For the same therapeutic index, trihexiphenidyl and benactizine were characterized by the maximum tolerance (TD50/ED50 > 10) in mice. Scopolamine and atropine exhibited anticonvulsant activity at doses exceeding the threshold values by a factor of 6.3 and 3.9, respectively. For procyclidine, the average anticonvulsant dose was threefold lower than the threshold value. Benactizine and procyclidine had maximum tolerance levels in rats. The TD50/ED50 ratio for these drugs was greater than 3 (against 0.5 - 0.7 in groups treated with trihexiphenidyl, atropine and scopolamine).


Subject(s)
Anticonvulsants/pharmacology , Maximum Tolerated Dose , Muscarinic Antagonists/pharmacology , Animals , Male , Mice , Rats
18.
Eksp Klin Farmakol ; 75(9): 21-4, 2012.
Article in Russian | MEDLINE | ID: mdl-23156083

ABSTRACT

The effect of an angiotensin receptor II antagonist (losartan) on the model acute renal failure (ARF) induced by severe ethylene glycol poisoning at 2/3 LD50 has been studied in rats. It is established that losartan administration (20 mg/kg for 72 h) produces a significant (4-fold) increase in the animal death rate, which is associated with ARF transition to a decompensation stage. Pronounced changes in the qualitative and quantitative composition of diurnal diuresis, more than 8-fold increase in the creatinine level, and 18-fold increase in the blood urea have been observed. Thus, the administration of losartan to ethylene glycol poisoned rats causes more pronounced degeneration of proximal tubule epithelium and destruction of glomeruli. It is concluded that the use of losartan for the treatment of ARF is inexpedient.


Subject(s)
Acute Kidney Injury/chemically induced , Acute Kidney Injury/drug therapy , Angiotensin II Type 1 Receptor Blockers/pharmacology , Ethylene Glycol/poisoning , Losartan/pharmacology , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Diuresis/drug effects , Glomerular Mesangium/metabolism , Glomerular Mesangium/pathology , Kidney Tubules, Proximal/metabolism , Kidney Tubules, Proximal/pathology , Male , Rats , Rats, Wistar
19.
Bull Exp Biol Med ; 152(3): 378-81, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22803091

ABSTRACT

A model of brain ischemia induced by staged ligation of the left and right common carotid arteries has been developed in experiments on rats. The use to this model led to reduction of animal mortality. On days 2-5 after the second ligature, the animals lost weight, the level of their CNS vulnerability increased, the volume of perceived information reduced, adaptation to environmental conditions and reproduction of conditioned reflexes were disordered. Focal and diffuse destructive changes in the nerve and glia cells were found in the cerebral cortex, hippocampus, and thalamic nuclei. The severity of disorders in the blood supply to the brain depended on the interval between ligation of the carotid arteries. This recommends this model for evaluation of the efficiency of drugs of various pharmacological groups.


Subject(s)
Brain Ischemia/physiopathology , Carotid Artery, Common/surgery , Cerebrovascular Circulation/physiology , Models, Animal , Animals , Brain/pathology , Carotid Artery, Common/pathology , Histological Techniques , Ligation/methods , Male , Rats
20.
Radiats Biol Radioecol ; 52(2): 175-80, 2012.
Article in Russian | MEDLINE | ID: mdl-22690580

ABSTRACT

The study was aimed at evaluating the radioprotective effectiveness of beta-estradiol following its prophylactic administration in conditions of acute irradiation. Evaluation of the radioprotective efficiency was performed by studying the 30-day survival rate, life expectancy, the structure of irradiated mice death, the bone marrow hematopoiesis using the method of exogenous colony formation. The prophylactic use of beta-estradiol at doses of 20 and 40 mg/kg 5 days before irradiation has been established to protect the exposed mice against radiation death induced by X-rays at doses LD50-90/30, thus increasing their survival rate by 17-58%, and to favor the reduced expression of post radiation disorders of bone marrow hematopoiesis.


Subject(s)
Bone Marrow/drug effects , Bone Marrow/radiation effects , Estradiol/administration & dosage , Hematopoiesis/drug effects , Hematopoiesis/radiation effects , Radiation-Protective Agents/administration & dosage , Animals , Male , Mice , Mice, Inbred C57BL , Radiation Dosage , Survival Rate , Whole-Body Irradiation , X-Rays/adverse effects
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