The study of the protective effect of mitochondrial uncouplers during acute toxicity of the fungicide difenoconazole in different organs of mice.

Pesticides represent a serious problem for agricultural workers due to their neurotoxic effects. The aim of this study was to evaluate the ability of pharmacological oxidative phosphorylation uncouplers to reduce the effect of the difenoconazole fungicide on mitochondrial DNA (mtDNA) of various organs in mice. Injections of difenoconazole caused cognitive deficits in mice, and the protonophore 2,4-dinitrophenol (2,4-DNP) and Azur I (AzI), a demethylated metabolite of methylene blue (MB), prevented the deterioration of cognitive abilities in mice induced by difenoconazole. Difenoconazole increased the rate of reactive oxygen species (ROS) production, likely through inhibition of complex I of the mitochondrial respiratory chain. After intraperitoneal administration of difenoconazole lungs, testes and midbrain were most sensitive to the accumulation of mtDNA damage. In contrast, the cerebral cortex and hippocampus were not tolerant to the effects of difenoconazole. The protonophore 2,4-DNP reduced the rate of ROS formation and significantly reduced the amount of mtDNA damage caused by difenoconazole in the midbrain, and partially, in the lungs and testes. MB, an alternative electron carrier capable of bypassing inhibited complex I, had no effect on the effect of difenoconazole on mtDNA, while its metabolite AzI, a demethylated metabolite of MB, was able to protect the mtDNA of the midbrain and testes. Thus, mitochondria-targeted therapy is a promising approach to reduce pesticide toxicity for agricultural workers.

The Relationship of p62 Gene Expression with Integrity of Mitochondrial DNA and the Level of Lipid Peroxidation Products in Skeletal Muscles of Rats of Different Ages Exposed to Different Feeding Protocols.

Sequestosome-1 (SQSTM1/p62) is one of the most important multifunctional proteins, which is necessary to maintain mitochondrial stability by eliminating damaged mitochondria through mitophagy. We studied the influence of age and diet on the expression of the p62 gene in the femoral and abdominal muscles of rats, as well as the integrity of some mitochondrial components. In the femoral muscles of 24-month-old rats receiving restricted ration, the expression of the p62 gene increased. We assume that activation of mitophagy contributed to a decrease in the levels of oxidative damage to mitochondrial DNA and LPO intensity in the femoral muscles of 24-month-old rats.

[The peripheral blood of frogs in the genus Rana as a test system for assessing environmental pollution]. / Perifericheskaia krov' liagushek roda Rana kak test-sistema dlia otsenki zagriazneniia okruzhaiushchei sredy.

Differential analysis of leukocytes was carried out peripheral blood smears of the frogs from four localities in the territory adjacent to a chemical plant in the Novgorod District (Rana temporaria) and two localities with an increased radiation background in the Bryansk District (R. lessonae and R. esculenta). Marked and similar changes in the content of neutrophilic and eosinophilic granulocytes were found in the frogs from all studied localities. A pronounced neutropenia was noted, which was often accompanied by the appearance of immature forms of the neutrophilic series. We propose that these changes are due selective damage of the entire series of differentiation of neutrophilic granulocytes, including the precursor cells. The increased percentage of eosinophilic granulocytes and appearance, in some cases, of immature cells are considered as signs of protective (antitoxic and antimicrobial) response.

[Comparative radioautographic study of 35S--sulfate and 3H-serotonin incorporation into the mast cells of a number of rodents]. / Sravnitel'noe radioavtograficheskoe issledovanie vkliucheniia 35S-sulfata i 3H-serotonina v tuchnye kletki riada gryzunov.

A comparative autoradiographic assay of 35S-sulphate and 3H-serotonin incorporation in the periotoneal mast cells was carried out for the rat, mouse, Syrian and striped hairy-footed hamsters. No marked specific differences between the mast cells of the animals under study by the intensity of radiosulphate incorporation were found. At the same time the capacity of 3H-serotonin binding was much higher in the mast cells of rats and mice, as compared with those of hamsters. When using the discovered differences as a species marker, one has to take into account the possibility of changing the mast cells' properties with respect to tissular environment.

[Dynamics of the restoration of a population of peritoneal mast cells following their destruction]. / Dinamika vosstanovlenniia populiatsii peritoneal'nykh tuchnykh kletok posle ikh razrusheniia.

Removal of the mast cells from the mouse abdominal cavity by repeated washings as well as their osmotic destruction with distilled water are suitable methods to study regeneration of mast cells in postnatal ontogenesis. Simultaneous application of their differential staining with alcian blue-safranin makes it possible to reveal successive stages of the newly formed mast cells maturation and determine duration of every stage. The time of complete renovation of the peritoneal mast cells has been stated to be, according to the mode of the stimulation, 60--80 days. Total duration of the first two stages of maturation is 1--2 days. Mast cell differentiation is fully completed by the 11th day.

[A radioautographic study of the turnover and differentiation of mast cells in normal mice and mouse radiation chimeras]. / Radioavtograficheskoe issledovanie obnovleniia i differentsirovki tuchnykh kletok u normal'nykh myshei i radiatsionnykh myshinykh khimer

The patterns of renewal of the previously labeled by 35S-sulphate mast cells of peritoneal liquor and loose connective tissue were investigated in normal mice, after their irradiation and transplantation of singenic and xenogenic bone marrow (radiation mouse chimaeras). The renewal of labeled mast cells in the peritoneal liquor proceeds markedly (ca. 10 times) more intensively than in the loose connective tissue. A stage of lymphocyte-like cells-precursors actively synthesizing sulphomucopolysaccharides is established in the series of differentiation of mast cells during postnatal ontogenesis. The duration of this stage amounts to 10-15 days. The patterns of renewal of the previously labeled by 35S-sulphate mast cells do not differ markedly in normal animals and radiation chimaeras.