[TOXICOMETABOLOMICS: DETERMINATION OF MARKERS OF CHRONIC EXPOSURE TO LOW DOSES OF ALIPHATIC HYDROCARBONS].

The metabolic profile of plasma of white non-linear rats was investigated under normal conditions and after chronic inhalational exposure to low doses of aliphatic hydrocarbons with the number of carbon atoms from 6 to 10. Metabolic profile was determined with combination of gas chromatography-mass spectrometry and high performance, high resolution liquid chromatography-mass spectrometry with subsequent use of chemometrical methods for data treatment and presentation. It was shown that continuous 90-day exposure to a mixture of C6-C10 saturated hydrocarbons at concentration of 160 ± 20.5 mg/m³ results in various impairments of metabolic processes in liver and kidneys. Exposure to hydrocarbons at doses of 31.4 ± 5.6 mg/m³ and 5.2 ± 1.8 mg/m³ evoked significantly smaller changes. Novel metabolic markers of the toxic effect of low concentrations of C6-C10 aliphatic hydrocarbons were revealed. The ratio of concentrations of pyrophosphoric and oxalic acids in rat blood plasma was found to be the most sensitive marker called <>. A hypothesis is put forward about the redox balance violation as the leading pathogenetic mechanism of neuropathies and concomitant pathologies associated with hydrocarbon chronic intoxication.

[INFLUENCE OF Ð -ENDORPHIN ON FUNCTIONAL ACTIVITY OF ISOLATED RAT HEART].

We have studied the effect of Р-endorphin (an endogenous opioid peptide) on the functional characteristics of isolated rat heart. In physiological concentrations (6.3 X 10-10 M) Р-endorphin induces a negative inotropic effect, accompanied by a slight decrease in the heart rate, and has no effect on the perfusion pressure of the coronary vessels. It is shown that the effect of Р-endorphin is mediated by 5-opioid receptors. ATP-dependent K+-channels contribute the greatest contribution to the implementation of the effect of Р-endorphin on the isolated heart of a rat. The role of voltage-dependent K+-channels and NO-mediated mechanisms in the implementation of the effects of Р-endorphin is minor.

Proteolysis of His-Phe-Arg-Trp-Pro-Gly-Pro in the blood and brain of rats in vivo.

The kinetics of the content of His-Phe-Arg-Trp-Pro-Gly-Pro (ACTH (6-9)PGP) and its hydrolysis products in the blood and brain of rats in the case of intranasal administration and intravenous injection of tritiated ACTH(6-9)PGP was studied. The parameters of bioavailability of ACTH(6-9)PGP administered intranasally were higher, indicating certain prospects in the intranasal application in clinical practice. We also found that the factor that determines ACTH(6-9)PGP proteolysis in experiments both in vivo and in vitro is aminopeptidases. The main products of ACTH(6-9)PGP during its metabolism in rats are short peptides and amino acids.

Penetration of thyroliberin in the blood and brain regions at intranasal or intravenous administration.

The maximum amounts of the thyroliberin in the blood and brain of rats at intranasal and intravenous administration were determined. It is found that rat hippocampal, cortical, and cerebellar membranes contain two types of specific binding sites (high- and low-affinity) for the labeled ligand. It was shown that, at intranasal and intravenous administration, maximum amounts of the thyroliberin were detected in the cerebellum and then in the cortex and hippocampus. The degradation of the thyroliberin in the rat brain and its regions at intranasal and intravenous administration was studied. It is shown that the degree of degradation and the formation of proteolytic products of the thyroliberin is different in different regions of the rat brain.

[The medical and sanitary passport of chemically hazardous facility and the surrounding area as the register of indicators of sanitary and epidemiologic safety of a state of health and habitat areas].

Basic provisions of the medical and sanitary passport of chemically dangerous object and the territory adjoining to it are presented in article. Need of development of the medical and sanitary passport for systematization of sanitary and epidemiologic data with the purpose of a complex assessment of health of the population and the personnel working at chemically dangerous objects, harmful factors production and environment taking into account emissions of polluting substances of chemically dangerous objects is shown.

[The urgency of the application of the medical sanitary passport in the system for chemical safety in the areas of location of high-risk chemical facilities in the Russian Federation].

The main provisions concerning the need for a creation of medical and sanitary passport for territories in the protective measures zones (PMZ) of storage facilities and facilities for the destruction of chemical weapons (FDCW) are presented in the article. The assessment of results of certification of the territory of PMZ and FDCW in "Maradykovsky" in the Kirov region has been done.

[The manifestations of toxicity of nanoparticles (a review)].

The analysis of the data available in the literature has shown that nanoparticles (NP) have a high toxicity than usual microparticles, can penetrate unchanged across the cell barriers, the blood-brain barrier into the central nervous system, circulate and accumulate in the organs and tissues, by inducing more significant pathomorphological lesions in the visceral organs, and have a long elimination half-life. The toxicity of HPs is determined by their shape and sizes; moreover, minute fusiform particles cause more destructive effects than similar spherical particles; upon exposure, there is a clear dose-effect relationship. According to exposure to NPs, the classical target organs for the latter are the lung, liver, kidney, brain, gastrointestinal tract.

[New approaches to early diagnosis of chronic organophosphorus chemicals intoxication in workers at chemical weapons extermination objects].

Mass spectrum analysis revealed differences in general contents of low-molecular peptides spectrums in chemical weapons extermination object staffers, in comparison with the reference group. Findings are that serum paraoxonase activity in chemical weapons extermination object staffers in significantly increased.

[Studies of interaction of intracellular signalling and metabolic pathways under inhibition of mitochondrial aconitase with fluoroacetate].

Mitochondrial aconitase has been shown to be inactivated by a spectrum of substances or critical states. Fluoroacetate (FA) is the most known toxic agent inhibiting aconitase. The biochemistry of toxic action of FA is rather well understood, though no effective therapy has been proposed for the past six decades. In order to reveal novel approaches for possible antidotes to be developed, experiments were performed with rat liver mitochondria, Ehrlich ascite tumor cells and cardiomyocytes, exposed to FA or fluorocitrate in vitro. The effect of FA developed at much higher concentrations in comparison with fluorocitrate and was dependent upon respiratory substrates in experiments with mitochondria: with pyruvate, FA induced a slow oxidation and/or leak of pyridine nucleotides and inhibition of respiration. Oxidation of pyridine nucleotides was prevented by incubation of mitochondria with cyclosporin A. Studies of the pyridine nucleotides level and calcium response generated in Ehrlich ascite tumor cells under activation with ATP also revealed a loss of pyridine nucleotides from mitochondria resulting in a shift in the balance of mitochondrial and cytosolic NAD(P)H under exposure to FA. An increase of cytosolic [Ca2+] was observed in the cell lines exposed to FA and is explained by activation of plasma membrane calcium channels; this mechanism, could have an impact on amplitude and rate of Ca2+ waves in cardiomyocytes. Highlighting the reciprocal relationship between intracellular pyridine nucleotides and calcium balance, we discuss metabolic pathway modulation in the context of probable development of an effective therapy for FA poisoning and other inhibitors of aconitase.

[Embryo- and genotoxic effects of two endosulfan forms in the culture of rat and mouse pre- and postimplantation embryos]. / Embrio- i genotoksicheskie éffekty dvukh form éndosul'fana v kul'ture do- i postimplantatsionnykh zarodyshei krysy i myshi.

We studied embryo- and genotoxic effects of two forms (powder and microcapsular) of organochlorine insecticide and acaricide endosulfan in rat and mouse cultures of pre- and postimplantation embryos. The substance caused embryonic death, teratogenesis, and inhibited embryonic growth. Embryo cultivation in the serum obtained from the rats 1-48 h after single peritoneal introduction of highest bearable endosulfan dose allowed us to compare time pattern of the embryotoxic factors in the animal blood for the both substance forms. Microcapsular endosulfan induced much later appearance of the embryotoxic factors in the rat blood, had lower embryolethal and teratogenic effects, but prolonged the presence of pathogenic factors in the animal as compared to the powder form. We propose that embryo- and genotoxic activity of endosulfan increases in the course of its biotransformation.

[Toxicological examination of new chemicals]. / Toksikologicheskaia ékspertiza novykh khimicheskikh veshchestv.

The authors consider the problem of the express study of new or scantily studied chemical compounds. The data received in short-term experiments allow not only to validate hygienic standards but also to evaluate the character of action of chemicals studied. The authors discuss the possibility of rejecting the determination of Lim(ac) in practice of validating Tentative Safe Exposure Levels in working zone air (TSELwz).