The Journal “Toksikologicheskiy vestnik” (Toxicological Review)
The safe application of drugs in medical practic is one of major tasks of public health services. To increase safety of conducting clinical trials, especially in case of the first prescription of a drug to the patient, a drug safe dosedefining algorithm is considered based on pre-clinical toxicologica studies.
Keywords: safety of drugs, toxicity effects, pre-clinical research, clinical trials
At acute intoxications with psychotropic medications (amitriptilyne, carbamazepine, clozapine, zopiclone), pharmacologically active and toxic metabolites such as epoxides and nitrogen-containing oxides (191 patients) accumulate at critical and lethal levels that leads to severe neurotoxic effects.
Keywords: acute poisonings, epoxides, nitrogen-containing oxides, psychotropic agents, toxicometry
Thе non-cholinolytic activity of muscarinic receptor blockers was studied in experiments after their intake in average effective doses based on convulsive disorder management following diisopropylfluorophosphate poisoning at 1 LD50 dose. The therapeutic intensity of atropine and trihexyphenidyl was lower than that of benactizine. Benactizine in threshold doses has inhibitory effect on animal behavior, whereas atropine and trihexyphenidyl produce excitant effect. Blockers of ACh receptors tested produce dophamine-blocking effect (trihexyphenidyl, atropine), adreno-stimulating (trihexyphenidyl, benactizine), N-cholinolytic (trihexyphenidyl) and M- cholinolytic (benactizine, atropine) actions.
Keywords: anticonvulsant activity, muscarinic antagonists, non-cholinolytic effects
Model-based testing of rats intoxication with diisopropylfluorophosphate in 1 LD50 dose was performed to investigate effectiveness of application of inhalation bronchial spasmolytics from a M-cholinolytics group (atropine, ipratropium bromide) and 2-adrenergic agonists (salbutamol, formoterol). The intake of bronchial spasmolytics in combination with a conventional atropine therapy (1 mg/kg, intramuscularly) lowered the severity of disturbances in external respiration and accelerated its recovery over 24h after intoxication. It was established that at organophosphorous intoxication, the 2-adrenergic agonists potentiating effect on external respiration occurs on account of increasing breathing capacity by 25-50% and cholinolytics therapeutic effect shows in growth of breathing capacity by 20 to 40%.and breathing rate by 10 to 15%. Of preparations investigated, formoterol (2μg /kg), and ipratropium bromide (170 μg/kg) proved to be the most effective as for intensity and duration of therapeutic effect. The both preparations stabilized pulmonary minute volume at the level of 70-80% against background values during the first 8 hours after intoxication.
Keywords: 2-adrenergic agonists, external respiration, inhalation intake, M-cholinolytics, organophosphorous compounds
Modes of action of active forms of oxygen (AFO) are presented. Cells of inborn immunity can generate relatively high concentrations of AFO to fight pathogens. At the same time, AFO low concentrations continuously evolve in all cells of the body and perform signal functions as secondary messengers in redox-sensitive signal pathways. Investigations into modulation mechanisms of intracellular homeostasis, role of endogenous and exogenous AFO sources are necessary to understand pathogenesis of diseases, action of pharmaceutical and toxic substances.
Keywords: oxygen active forms (AFO), calcium, cytotoxicity, hydrogen peroxide, intracellular signaling, kinases
Results of influence of exposure to heavy metals (chrome, cadmium, zinc, lead) and polychlorinated biphenyls in doses corresponding to threshold values for the immune system in chronic experiment are described in this article. It was determined that investigated chemicals had immunosuppressive effects on the immune system including decrease in concentrations of IgA and IgE in serum and absence of mitogen-stimulated proliferation of immune cells. MTT-test can be recommended to study the immune system adaptation mechanisms ae well as negative impact of chemicals exposure.
Keywords: heavy metals, immunoglobulin, MMT-test, polychlorinated biphenyls
Present-day ideas about in vitro and in vivo transformation of V-type oraganophosphorus chemical agent are described. In vitro experiments, a new covalent RVX adduct with blood plasma proteins was identified using HPLC with tandem mass-selective detection in high resolution mode. Data were obtained to evaluate albumin input into RVX detoxification process.
Keywords: adduct, albumin, binding, plasma, RVX
Examples of optimization are considered of a new approach to toxicological analytical screening of biological fluids in patients with various symptoms of acute intoxication. The procedure used includes head-space solid-phase micro extraction of vapor components over blood and urine samples and extracts of the samples treated with derivatizing agents, analyzed by chromatography–mass spectrometry (GCMS) and automated interpretation of resulting mass chromatograms. The developed approach features a combination of head-space analysis of volatile compounds and analysis of derivatized extracts. The use of different derivatizing agents favors a more reliable identification of volatile compounds without using reference compounds. The key advantage of the proposed screening procedure is that it combines high throughput due to automated processing and interpretation of GCMS data and reliability due to reduced probability of both first- and second-type mistakes.
Keywords: biomedical samples, derivatization, GCMS, solid-phase extraction, toxicological screening
The influence of Mercury intake with feed (0.17 mg/ Hg/kg feed) on feeding behavior and serotonine level in carp fingerlings brain was investigated over 8 weeks. By the end of the experiment, the Hg concentration increased 4,9-folds in muscles and 8-folds in brain. Under Hg influence, the time of fishes staying in the initial test chamber increased by 20% and time to attain the feeder increased by up to 5.6 times. Feed allowance decreased by 38%. The impact of Hg at the serotonine level in the fish intact brain is expressed slighter than that on feeding behavior. The indicator shows a tendency to increasing 2 and 6 weeks after the beginning of the experiment (by 6% and 14% correspondingly). The last case is authentic. Results obtained give evidence of the most expressive negative influence of Hg on carp motor responses and feeding intensity and to a lesser extent on serotonine level in brain. Potential mechanisms of Hg toxic exposure on behavior responses and serotonine level in fish brain are examined.
Keywords: carp, feeding behavior, merciry, serotonine