The Journal “Toksikologicheskiy vestnik” (Toxicological Review)
Results of experimental studies are reported that made it possible to establish decrease in sensitivity and the development of toxicological tolerance (addiction) to the anti-tuberculosis drug “Isoniazid” repeatedly administered to laboratory animals in toxic doses and to determine growth rate of the toxicological tolerance development, maximum and average life expectancy, severity of seizures .
Keywords: anti-tuberculosis preparation, isoniazid, toxicological tolerance (addiction), convulsions, epileptic status, lethality, life expectancy, rate of addiction development, rational chemotherapy, experimental studies
Airborne Fe2O3 nanoparticles (NPs) with the mean diameter of 14±4 nm produced at spark ablation from 99.99% pure iron rods were fed into a «nose-only» exposure tower for rats exposed for 4 h a day, 5 days a week during 3, 6 or 10 months at a mean concentration of 1.14±0.01 mg/m3. Nanoparticles filtered out of the air exhausted from the exposure tower proved insoluble in de-ionized water but gradually dissolved in the cell free fluid supernatant produced by broncho-alveolar lavage and in the sterile bovine blood serum. The Fe2O3 content in lungs was measured by the Electron Paramagnetic Resonance (EPR) spectroscopy. NP retention in lungs and in brain was visualized with the Transmission Electron Microscopy (TEM). It was found a relatively low but significant pulmonary accumulation of Fe2O3, gradually increasing with time but tending to attain an equilibrium level. Besides, TEM-images showed nanoparticles retention within alveolocytes and the myelin sheaths of brain fibers associated with their ultrastructural damage. A multi compartment system model was developed and identified which describes toxicokinetics of inhaled nanoparticles after their deposition in the lower airways as a process controlled by their (a) high ability to penetrate through the alveolar membrane; (b) active endocytosis; (c) in vivo dissolution. However, in this particular study, dissolution-depending mechanisms proved to be dominant due to the rather high solubility of the finest Fe2O3-NPs in biological milieux.
Keywords: iron oxide nanoparticles, toxicokinetics, system modeling
In an organotypic culture, an investigation was conducted into combined effects of cyclophosphamide DNA as synthesis inhibitor used to model a resorptive action of mustard gas, and cortexin polypeptide or each of 20 encoded amino acids on the development of cell proliferation in cerebral cortex explants of the rat. The combined administration of cyclophosphamide together with cortexin or with each of the 20 encoded amino acids, except glycine, showed suppression of the cytostatic agent inhibitory effect. Thus, cortexin and amino acids have a protective effect on cell proliferation in the tissue culture of the central nervous system under the action of mustardlike substances.
Keywords: Cyclophosphamide, amino acids, polypeptides, tissue culture
The review sets forth perspective directions of correction of neurotoxic disorders in case of carbon monoxide damage. It was shown that carbon monoxide intoxication, in addition to the development of hemic hypoxia, leads to indirect lesions in the structures of the central nervous system that develop both in the early and delayed periods of poisoning. Those lesions can be caused by the development of oxidative stress, activation of programmed cell death, impact on the intercellular signaling system etc. There is evidence that oxygen monotherapy does not lead to a complete recovery of cognitive functions in a delayed period of severe carbon monoxide poisoning. It was found out that to correct central nervous system functions disorders in case of acute damage by carbon monoxide, it is necessary to use agents possessing neuroprotective mechanisms of action. The review reports data on the effectiveness of hydrogenated solution, methane solution, allopurinol, erythropoietin, granulocyte colonystimulating factor, remifentanil, mesenchymal stem cells, cerebrolysin for correction of the central nervous system disorders in this type of pathology.
Keywords: carbon monoxide, neurotoxicity, oxygen, neuroprotection, hydrogenated solution, allopurinol, erythropoietin, granulocyte colony-stimulating factor, mesenchymal stem cells, cerebrolysin
Results of the analysis of cytogenetic effects of lead ions on polytene chromosomes of Glyptotendipes glaucus Mg are reported. The functional state of polytene chromosomes was determined via computation: chromosome compactness index (CR); coefficient of genetic activity of the nucleolar organizer (NOR) and coefficient of genetic activity of the Balbiani ring (BR). With increase of the lead nitrate solution concentration, the compactness index increases, that is, the chromosomes compactness decreases: medians of CR values (when measuring shoulder E) in the control are 6.05, for the maximum concentration studied they are 7.3. As a result of the of lead ions action, the activity of the nucleolar organizer genes decreases: medians of the NOR values decrease from 2.3 in the control to 2.0 for the highest concentrations used in the experiment. The activity of the Balbiani ring genes increases with the growing concentration of the lead nitrate solution: medians of the BR values in the control are 1.45, for the maximum studied concentration they are 1.95. The G. glaucus genome responds ambiguously to the change in the lead ions concentration in the medium: the coefficient of the nucleolar organizer’s genetic activity decreases, while the genetic activity of the Balbiani ring, on the contrary, increases.
Keywords: heavy metals, polytene chromosomes, chironomidae, genetic activity
On the models of acute hemic and acute histotoxic hypoxia, the activity of a new complex compound of 5-hydroxy- 6-methyluracil with sodium succinate was studied. It was found out that the compound under investigation in respects to its activity is comparable or superior to reference preparations-reamberin, sodium succinate and oxymethyluracil, and has low toxicity at intragastric and intraperitoneal administration to mice. Based on the results of the studies, the patent of the Russian Federation was awarded.
Keywords: hypoxia, complex compound of 5-hydroxy-6-methyluracil with sodium succinate, anti-hypoxic activity, toxicity
The results of a comparative analysis of some blood serum immune-biochemical indices of bream that inhabits lake Nero and the Rybinsk Reservoir are reported. The following indices were investigated: anti-microbial properties: proportion of immune-deficient animals, common lipids level and their fractional composition, content of malondialdehyde and antioxidant activity. Unlike fishes from relatively clean waters, fishes from ecologically unfavorable areas show low immune status, alterations in lipid metabolism and increased free radical oxidation.
Keywords: Lake Nero, the Rybinsk reservoir, bream, immunity, lipids, oxidation processes
Strain Pseudomonas aureofaciens BKM-2391Д recovered from the soil arounel oat rhizosnhere is not a genetically modified strain. Based on investigations performed, the following hygiene norms are recommended for the strain Pseudomonas aureofaciens BKM-2391Д: MAC occupational air , Mark A on the level of 5х103 , hazard class 3 taking into account safety coefficient of 10 for occupational air; MAC atmospheric air, Mark A on the level of 5x102cells/ m3, Mark A, hazard class 3 taking into account safety coefficient of 100 for residential areas. These values of hygiene standards recommended for approval are in compliance with previously approved standards (MAC occupational air , 5000cells/ m3, MAC atmospheric air 500 cells/ m3 for various strains P.aureofaciens B-4117, P.fluorescens B-6844, P. fluorescens(denitrificans) B-99 and others.
Keywords: microorganism, toxicity, hazard