[Antioxidant enzymes and lipid peroxidation in C57Bl/6 and BALB/c mice].
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Animals↗
Biomedical subjects
A D Durnev
Publications and source records attributed to A D Durnev.
Comparative investigation of anticlastogenic effects in cell cultures of healthy donors and patients with nettle-rash.
In cultures of lymphocytes from 12 healthy donors and 12 patients with nettle-rash (NR) the anticlastogenic effect of the antimutagens WR-2721 (WR), bemitil (BM), tomerzol (TM) and interferon (IF) on the induction of chromosomal aberrations by photrin (PT) and dioxidine (DX) was investigated. There were no statistically significant differences between healthy donors and patients with NR in the levels of chromosomal aberrations that were spontaneous or induced by PT or DX. Statistically significant protective effects of BM, WR, TM and IF were demonstrated in cells of healthy donors after treatment with PT or DX, and after modification of the clastogenic action of PT in lymphocytes of NR patients. There was no protective effect of any of the anticlastogens after treatment of the lymphocyte cultures from NR patients with DX. That observation allows us to suggest the test of anticlastogenic action as a measure of sensitivity of the chromosomal apparatus in groups with different genetic risks.
Amifostine↗
[Antimutagenic properties of ubiquinone-10].
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Animals↗
Peculiarities of the clastogenic properties of chrysotile-asbestos fibers and zeolite particles.
It has been established that chrysotile-asbestos fibers and zeolite particles induce chromosome aberrations in human lymphocytes from whole blood cultures, peritoneal fluid cells and bone marrow cells of mice. It is shown that the level of cytogenetic response from the intraperitoneal administration of chrysotile-asbestos fibers and zeolite particles depends on the time of their exposure. Further, it is shown that SOD eliminates the cytogenetic effect of chrysotile-asbestos fibers, while catalase inhibits that of zeolite particles. Recommendations concerning testing for the mutagenic properties of mineral fibers and particles are given, and possible mechanisms of their damaging effects are discussed.
Animals↗
[The pharmacological problems of searching for and using antimutagens].
To design protectants of human genomic structures against mutagenic effects is defined as a new pharmacological problem; the perspectives of its solution are outlined. The experimental evidence that formed the biological basis for searching for pharmacological correctors of the mutagenic effects produced by xenobiotics is analysed, the basic principles for designing pharmacological protectants of genetic structures are formulated. Great emphasis is laid on the antimutagenic properties of antiradical agents. Evidence is provided for that there are no prospects of searching for pharmacological protectants among natural and synthetic phenol compounds. It is noted that the informative value of microbiological tests is poor. To design a corrector of the damaging action of each particular mutagen is shown to be an independent scientific problem which can be solved only by employing eukaryotic test systems. The areas of possible application of antimutagens are defined and some known examples of their use to protect human genetic structures are presented.
Antimutagenic Agents↗
[Remote effects in the mutagenic action of chrysotile asbestos and zeolite dusts in vivo].
It was proposed that there are a generalized mutagenic actions of chrysotile-asbestos fibers and zeolite particles in vivo. Chrysotile-asbestos fibers and different species zeolite particles in doses 50 mg/kg, intraperitoneally, increased the levels of damaged chromosomes not only in peritoneal cells, but also in bone marrow of C57BL/6 mice. Cytogenetic effect of chrysotile-asbestos does not depends on the time exposure of animals with mutagenic factor. In four weeks followed after administration chrysotile-asbestos fibers there were revealed 19-22% peritoneal cells with damaged chromosomes and 3.2-4.4% aberrant cells of bone marrow. Cytogenetic effect of zeolite particles was observed on 14-28 days after the administration, with peaks at 35.6% in peritoneal and 3.6-4.2% in bone marrow cells. Our data indicate the mutagenic action is realised as in cells contacted with dusts as in cells of other tissues. Probably, these effects are mediated by products of lipid peroxidation.
Animals↗
Oxygen radical-mediated mutagenic effect of asbestos on human lymphocytes: suppression by oxygen radical scavengers.
The mutagenic effect of chrysotile asbestos fibers and zeolite and latex particles on human lymphocytes in whole blood has been studied. It was concluded that their mutagenic activities were mediated by oxygen radicals because they were inhibited by antioxidant enzymes (SOD and catalase) and oxygen radical scavengers (rutin, ascorbic acid, and bemitil). It was proposed that oxygen radicals were released by phagocytes activated upon exposure to mineral dusts and fibers. The study of lucigenin- and luminol-amplified chemiluminescence of peritoneal macrophages stimulated by chrysotile fibers and zeolite and latex particles has shown that their mutagenic action is probably mediated by different oxygen species, namely, by the iron-oxygen complexes (perferryl ions) plus hydrogen peroxide, hydrogen peroxide, and superoxide ion, respectively. From the oxygen radical scavengers studied, rutin was the most effective inhibitor of the mutagenic effect of mineral fibers and dusts.
Animals↗
[The mutagenic action of the dust of natural zeolites and chrysotile asbestos].
The cell chemiluminescence method was used to demonstrate the ability of asbest and zeolite dusts from 8 deposits of the USSR to induce generation of free oxygen radicals in the phagocytosing cells suspension. It has been found that asbest and zeolite (0.01 and 0.05 mg/ml) increase levels of cells with chromosome aberrations in human cell cultures. The cytogenetic effect of asbest was inhibited by superoxide dismutase (50 mg/ml). The damaging effect of zeolite was decreased by the pharmacological drug bemithyl (0.007-0.07 mM) and completely eliminated by catalase (20 mg/ml). The results obtained indicate that mutagenic effect of dust particles of asbest and zeolite is mediated by oxygen radicals.
Aluminum Silicates↗
[Mutagenic and antimutagenic properties of bemitil].
Complex research of the genetic activity of a new 2-mercaptobenzimidazole derivative bemythyl has shown that the drug failed to induce recessive, age-related lethal mutations in drosophila, dominant lethal mutations in germ mammalian cells and chromosomal damage in murine bone marrow cells and human peripheral blood cell cultures. The experiments on mice have demonstrated that therapeutic bemythyl doses caused a two-fold decrease in the level of aberrant cells induced by alkylating agents--fotrin and fopurin.
Animals↗
[Effect of emotional stress on the frequency of chromosome aberrations in the bone marrow cells of mice].
The chromosome aberration rate was studied in bone marrow cells of C57BL/6, CBA and BALB/c mice before and after emotional stress. After "the opened field" experiment the chromosome aberration rate in C57BL/6 and CBA mice increased while that in BALB/c mice remained unchanaed. The mutagenic effect was prevented by phenazepam.
Animals↗
Antimutagenic activity of crown-containing compounds.
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4-Nitroquinoline-1-oxide↗
[The influence of verapamil on the clastogenic effect of cyclophosphane in somatic cells from BALB/c and C57Bl/6 mice].
The method of chromosome aberration count in the bone marrow cells of male BALB/c and C57Bl/6 mice was used to study the influence of intraperitoneal injection of verapamil in doses of 0.1-10 mg/kg and its administration into the stomach in doses of 2.5-10 mg/kg on the clastogenic effect of cyclophosphamide (10 mg/kg intraperitoneally) in a single and repeated (5 times at intervals of 24 h) administration. In repeated administration in all the doses used, verapamil significantly intensified the mutagenic activity of cyclophosphamide in C57Bl/6 mice and in doses 10 mg/kg in BALB/c mice. A single intraperitoneal verapamil injection (0.1-0.4 mg/kg) caused a statistically increase in the clastogenic effect of cyclophosphan in mice of both strains. The same effect was encountered in intraperitoneal injection (2.5 mg/kg) and administration into the stomach (5 mg/kg) of the calcium antagonist in BALB/c mice. Thus, the effect of verapamil on cyclophosphamide clastogenic activity depends on the dose, method, and schedule of administration of the calcium antagonist.
Animals↗
[The antimutagenic activity of aspartame].
The method of chromosome aberration count in the bone marrow cells of C57B1/6 mice was used to study the influence of aspartame on the cytogenetic effects of dioxydin and cyclophosphan. Aspartame (0.4-40 mg/kg) was found to possess antimutagenic properties in relation to the listed mutagens. The discovered antimutagenic activity of aspartame was manifested more when it was injected for 5 days before the administration of a mutagen, whereas in joint administration of aspartame with the mutagens, the substitute for sugar did not change the clastogenic effect of dioxydin and cyclophosphan.
Animals↗
[The effect of bemetil on the production of DNA antibodies in patients with systemic lupus erythematosus].
The levels of autoantibodies against DNA in blood serum and severity of the disease were evaluated prior to, during, and after 8-week treatment of patients suffering from lupus erythematosus systemicus (LES) with prednisolonum (daily dose of 5-60 mg/kg, 15 patient) and with prednisolonum in combination with cyclophosphane (CP) (a total dose of 2-4 mg/kg per os. 15 patients), or bemithyl doses of 500-750 mg/day per os (15 patients) or bemithyl in combination with CP (the same doses, 16 patients). It was shown that introduction of bemithyl into LES treatment schedule significantly lowered the level of autoantibodies against DNA evaluated in immunoassay and reduced LES severity assessed using standard SLEDAI-1 and ECLAM scales.
Adjuvants, Immunologic↗
[The antimutagenic activity of afobazol studied in vivo].
The chromosome aberration assay in the bone marrow cells of C57B1/6 mice showed that the new 2-mercaptobenzimidazole derivative afobazole(1-100 mg/kg) prevented manifestations of the clastogenic effects of dioxidine (100 mg/kg, i.p.) over a period of 24 h and reduced by 44-75% the cytogenetic effect of dioxidine (300 mg/kg, i.p.). The same doses of afobazole produced a statistically significant decrease in the cyclophosphamide (20 mg/kg, i.p.) damage over a period of 24 h. Afobazole showed no inherent mutagen activity and did not potentiate the effects of mutagens studied.
Animals↗
[The use of the fluorimetric method for studying DNA integrity exemplified by an assessment of dioxidine genotoxicity].
The genotoxic effect of dioxidine (300, 100, 30, and 10 mg/kg, i.p.) on the liver cells of outbred male rats was studied by fluorometric analysis of DNA unwinding (FADU) using the cell DNA samples taken from animals sacrificed 1, 6, 18, and 24 h after drug introduction. At a dose of 10 mg/kg, dioxidine produced no statistically significant increase in the amount of DNA damage relative to control. Increase in the dioxidine dose to 30 mg/kg resulted in a significant DNA damage 1 h after drug administration, while a dose of 100 or 300 mg/kg reliably caused damage at all times of exposure.
Animals↗
[Modification by lacidipine of the clastogenic effect of dioxidine in vivo].
The influence of lacidipine (0.1-10 mg/kg, intragastric) on the clastogenic effect of dioxidine (100 and 200 mg/kg, i.p.) under conditions of their single and repeated (five-fold, 24-h interval) administration was studied by the chromosome aberration assay in the metaphase bone marrow cells of BALB/c and C57BL/6 male mice. It was found that single (5 or 10 mg/kg) and repeated (10 mg/kg) introduction of lacidipine enhances the clastogenic effect of dioxidine in both genotypes. At the same time, a single treatment of C57BL/6 mice with 0.1 and 1 mg/kg of lacidipine sometimes significantly reduced the clastogenic effect of dioxidine (200 mg/kg). Thus, lacidipine exhibits a comutagen effect in vivo when administered at large doses (5 and 10 mg/kg) but not at small doses, where the drug sometimes acted as antimutagen in C57BL/6 mice.
Animals↗
[Various mechanisms of the depriming effect of bacterial endotoxin on drug metabolism].
The effect of an endotoxin from Sh. Boydii on the biotransformation of amidopyrine and acetanilide, the activity of microsomal monooxygenases, hemoxygenase, and xanthine oxidase, the lipid peroxidation (LPO) intensity, the phospholipid spectrum, and the solubilization of microsomal membrane components was studied by intraperitoneal injections (2.5 mg/kg) in rats. It was found that the endotoxin inhibits the reactions of C- and N-acetanilide hydroxylation, N-amidopyrine demethylation, acetanilide hydrolysis at the amide bond, conjugation of aminophenol metabolites with glucuronic acid and sulfate, and 4-aminoantipyrine binding to acetate. The endotoxin effect reached maximum 24 h after injection and was observed for 96 h. The inhibition of metabolism of the test preparations is related to a decrease in the content of cytochrome P-450 and in the activity of 1A2, its 2B, 2C, 3A, and 2E1 isoforms. This is obviously caused by activated LPO and enhanced nitric oxide synthesis, as evidenced by a tenfold increase in the content of NO metabolites (nitrites and nitrates) in the blood of test animals. In clinical practice, it is necessary to take into account the possibility of a significant biotransformation of drugs in the acute period of bacterial infection, which may lead to changes in the pharmacological effect and toxicity of some drugs.
Acetanilides↗