The Journal “Toksikologicheskiy vestnik” (Toxicological Review)
Are presented summarized experimental data found out in previous years at the Institute of Biophysics on toxicokinetics, toxicometry and toxicodynamics of perchlorates and on the assessment of their hazard at peroral administration. Entering the body, perchlorates are rapidly absorbed by blood, undergo hydrolysis releasing a stable anion ClO4. They spread uniformly and are execrated with urine over two days. They are referred to moderately and low toxic substances as to absolute toxicity (LD50) and if based on the «acute action zone» parameter, to substances having a low ability to develop lethal and acute forms of poisoning (classes 3,4). A clinical intoxication picture is determined by a local irritation effect common to cations of these salts, general toxic manifestations and single-type specific antithyroid effect which is a pathogenic indicator of the ClO4 anion action. The latter allows to consider thyroid glands as targetorgan and the disturbance of its function as a limiting indicator of chlorine salts effect on the organism. Long exposures to perchlorates lead to an evident functional accumulation with the development of the thyroid gland hypertrophy, goitrogenous effect, stochastic effect, neurohumoral manifestations which classify them as extremely and high hazardous chemicals (class 1 and 2) according to «biological action zone».
It was established in experiments in noninbred white mice that the chronic intoxication by organophosphorus compounds and Russian VX and Sarin (total dose of 0.6 LD50, 60 days) equally reduces immune responses bound to Th1- and Th2 lymphocytes functions and concentration of cytokines IFN , IL-2, IL-4, IL-6; it does not affect the maintenance of IL-10 concentration in blood. At an organophosphorus exposure over 30 days the concentration of corticosteronum in blood increases and after 60 days substantially decreases.
An author’s morphometry method for human blood lymphocytes nuclei ready for micronucleated testing is described. The investigation includes the evaluation of genotoxic activity of a standard N-methyl-Nnitro-nitrosoguanidine mutagen at a concentration of 5.1-40.8 μM/ml in micronucleated test in human blood culture .A number of morphometric indicators of binuclear lymphocytes nuclei were determined in parallel. It was shown that cytogenetic indicators of genome instability correlate with changes in nuclei asymmetry extent and size. The feasibility of the developed morphometric analysis for fast forecasting of genotoxic effects is demonstrated.
The content of free SH-groups in rat and human blood plasma was determined by a modified Boyer method. It was found out that mercury influences the content of free sulfuric hydril groups in blood (plasma)- the higher mercury content, the lower concentration of free SH-groups is.
The incidence of the pneumonia development as complication following peroral poisonings by psychopharmacological preparations and lethality in patients who received a basic therapy and additional enteral detoxification of the organism is analyzed. It was shown that the application of a complex of enteral detoxification of the organism consisting of intestinal lavage, enterosorption and stimulation of the intestine using serotonin adipinate, contributes to decreasing the incidence of the pneumonia development 3.2- and 2.2. fold at mid-severe and severe poisonings correspondingly, and lethality from pneumonia decreases by more than 8.4 –fold.
Results of a toxicological investigation of nanoparticulate silver-and isoniazid-based nanocomposite to cure drug-resistant tuberculosis are presented. The investigation was conducted in nonlinear white mice and rat males. Acute and sub-acute chronic toxicity of the preparation was studied. It was established that silver nanoparticles do not change isoniazid toxicological characteristics. Results obtained determine parameters of a safe use of the proposed nanocomposite in pre-clinical investigations and its possible clinical studies.
At a single intraperitoneal administration, ENAP at a dose of 12.5 mg/100g animal’s body weight causes disturbances in strength and speed of isolated isovolumicly-contracting heart, inhibits energy metabolism in myocardium. The said changes manifest more expressively under conditions of high frequency cardiac stimulation, hypoxic perfusion and reperfusion.
Sunburn-preventing preparations are studied in relation to the content of titanium dioxide nanoparticles in their composition. For the first time it was shown that the composition of sun-screen creams contains two crystalline forms of titanium dioxide nanoparticles - rutile and anatase. The anatase nanoparticles are less than 25nm in size and therefore they can produce a toxic action on the organism.
A references-based analysis and own authors’ studies outcome allowed to develop a classification of chemical compounds producing a depriming effect. The systemization of depriming substances shows at least two deprimaton variants worth of speaking. Chemical compounds able to deprime the CNS functions for account of their effect on mechanisms of generating, conducting and transferring nerve impulses are allocated to primarily depriming agents. Compounds which depriming effects are bound to the development of typical pathologic processes (hypoxia, decrease in neurons power supply, disturbance in the electrolytic balance, micro circulation) are secondly depriming agents
The effect of potassium dichromate in doses from 1 to 100 mg Cr/l was tested over 180 days in fish species used in bio testing: guppy (Poecilia (Lebistes) reticulata аnd Danio rerio (Brachydanio rerio). Guppy appeared more resistant to the chronic exposure to the toxicant at low concentrations, while danio was resistant to higher concentrations at relatively short exposure. LC50 was 57.3 mg Cr/l for guppy and 75.7 mg Cr/l for danio during 96 h exposure and after 30 days 13 mg Cr/l for guppy and 47 mg Cr/l for danio. Changes in size growth, weight, morphologic characteristics in fishes exposed to Chromium were noted.
The impact of the mercury accumulation in the organism on the activity of glycosidasas ( -amylase, succharase, maltase, amylolytic activity) was investigated in vitro in the mucous membrane and intestinal content of the common shrew. A larger accumulation of mercury was shown in muscles, liver and intestine of specimens inhabiting poachy bio bogs. The activity of .glycosidasas in chyme changed more substantially with the increase of mercury content than the enzymes activity in the mucous membrane. Kinetic characteristics of disaccharides hydrolysis showed an increasing binding affinity of enzymes to the substrate which testifies adaptive changes of this indicator with the growth of mercury accumulation in the intestine.