We studied the effectiveness of Xe/O2 mixture inhalation (30% Xe and 70% O2, 20 min for 5 days) in a model of experimental thromboplastin pneumonitis. Inhalation of the studied mixture decreased the intensity of the inflammatory process in the lung tissue assessed by the temperature response of animals, changed lung weight and lung weight coefficient. At acute stage of pneumonitis, an increase in xenon consumption was recorded due to its retention in the gas exchange zone and a natural decrease in oxygen consumption due to partial alveolar/capillary block. The formation of pneumonitis was accompanied by a pronounced procoagulant shift in the regulation system of the aggregate state of blood. The Xe/O2 inhalations ensured physiologically optimal levels of prothrombin and activated partial thromboplastin time against the background of a moderate decrease in fibrinogen level throughout the experiment. At the same time, the activity of the natural anticoagulant antithrombin III increased from day 5 to day 14.
We studied the effect of an anthocyanin-containing complex from the fruits of S. aucuparia L. on doxorubicin-induced genotoxicity in bone marrow cells of C57BL/6 mice. The complex reduced the genotoxic effect doxorubicin in metaphase plates of bone marrow cells in 24, 48 h, and 10 days after the administration of the cytostatic. The mean number of single fragments and the fraction of cells with gaps and aberrant metaphases also decreased.
Anthocyanins are flavonoid compounds belonging to the group of polyphenols. A. melanocarpa ( Michx. ) Elliott chokeberry is known to be rich in these bioactive substances. The previously conducted chemical analysis showed that an anthocyanin-containing complex obtained from A. melanocarpa fruits comprise anthocyanins, flavonoids, phenolic acids, and catechins, with anthocyanins being the dominant components. A large amount of data indicates that Aronia fruits exhibit a wide spectrum of pharmacological activity. In this work, we assess the safety of an anthocyanin-containing complex obtained from A. melanocarpa fruits by its genotoxic study followed by an analysis of its effect on mutagenesis. To this end, a model of doxorubicin-induced genotoxicity in bone marrow cells of C57Bl/6 mice was used. The plant complex under study at a dose of 225 mg/kg had no effect the cytogenetic parameters of animal bone marrow cells after a single or double administration. The use of the anthocyanin-containing complex led to a decrease in DNA damage caused by the administration of doxorubicin, 24 and 48 hours after the introduction of a cytostatic agent. Hence, the data obtained can serve as the basis for the creation of a drug corrector for cycplasms.
The study aims to analyze furocoumarin extracts isolated from poison hemlock cell culture influencing the correction of cisplatin-caused cytostatic myelosuppression. The experiments were carried out on 160 CD1 female mice weighing 18–25 g. Cytostatic myelosuppression was simulated by administering cisplatin intraperitoneally once at a maximum tolerated dose of 10 mg/kg. The control group received physiological saline injections. Poison hemlock (Conium maculatum L.) cell culture extract was administered at a dose of 30 mg/kg to prevent the development of disorders. 4 mg/kg of Warfarin Nycomed was used for comparison examination. The correctors were administered intragastrically on the sixth day after cisplatin injected for four days. The indicators were examined on the 1st, 2nd, 5th, 7th, 10th, 15th, 20th and 30th days following the administration of cisplatin. The bone marrow and peripheral blood values were examined using the standard method. Statistical analysis was carried out using Stat Plus Pro (build 7.3.0.0). Under conditions of cytostatic myelosuppression caused by the administration of 10 mg/kg (maximum tolerated dose) of cisplatin, the use of the poison hemlock cell culture extract contributes to the restoration of myeloid and erythroid hematopoietic germs, as well as the normalization of bone marrow and peripheral blood values. With increase in the number of mature neutrophils and lymphocytes, erythroblasts, and normoblasts, the total number of myelokaryocytes increased. The content of erythrocytes and leukocytes increased in the peripheral blood as the number of segmented neutrophils and lymphocytes increased. The dynamics of hematopoietic sprout recovery with poison hemlock cell culture extract are similar to those of Warfarin.
The genotoxic effect of paclitaxel on the chromosomal material of differentiated bone marrow cells in male and female mice was revealed in the early and long-term periods of the study. It was found that during the same observation period paclitaxel causes bone marrow hypoplasia and reduces the number of early erythropoiesis progenitor cells in the bone marrow of experimental animals, and also contributes to a decrease in their proliferative potential regardless of gender.
Выявлено генотоксичное воздействие паклитаксела на хромосомный материал дифференцированных клеток костного мозга самцов и самок мышей в ранние и отдаленные сроки исследования. Установлено, что в эти же сроки наблюдения паклитаксел вызывает гипоплазию костного мозга и снижает в костном мозге экспериментальных животных количество ранних клеток-предшественников эритропоэза, а также способствует уменьшению их пролиферативного потенциала независимо от пола. The genotoxic effect of paclitaxel on the chromosomal material of differentiated bone marrow cells in male and female mice was revealed in the early and long-term periods of the study. It was found that during the same observation period paclitaxel causes bone marrow hypoplasia and reduces the number of early erythropoiesis progenitor cells in the bone marrow of experimental animals, and also contributes to a decrease in their proliferative potential regardless of gender.
The induction of cisplatin mutations was studied in female Drosophila carrying yellow, white, singed marker mutations on the same chromosome when crossed with wild-type males Canton-S.
Исследована индукция мутаций цисплатином у самок дрозофил, несущих маркерные мутации yellow, white, singed в одной хромосоме, при скрещивании с самцами дикого типа Canton-S. The induction of cisplatin mutations was studied in female Drosophila carrying yellow, white, singed marker mutations on the same chromosome when crossed with wild-type males Canton-S.
Introduction. Thrombotic complications caused by the tumor and consequences of its treatment are the leading causes of death in cancer patients. The development of a model for the pathology of hemostasis, in particular the excessive pathological clot formation, in the laboratory animals receiving antitumor agents, could help find new pharmacological methods for correcting hemostatic disorders.The purpose of the study was to study the effect of cisplatin on the blood coagulation system in mice and rats.Results. An experiment using outbred mice showed that the levels of PT-INR and aPTT were decreased and the level of fibrinogen was increased on day 10 after administration of cisplatin in the maximum tolerated dose of 10 mg/kg. A significant decrease in the PT-INR and aPTT levels was observed on day 15 after cisplatin injection only in female mice. The cisplatin injection at a dose of 4 mg/kg resulted in a decrease in the PT-INR, and aPTT levels and an increase in fibrinogen concentration on day 10. In rats, a significant decrease in the PT and aPTT levels was observed in both females and males on day 15 after cisplatin injection.Conclusion. A change in the PT and NIR, aPTT levels towards decrease and fibrinogen concentration towards increase indicates the initiation of thrombus formation.
Paclitaxel in a single MTD of 40 mg/kg caused chromosome aberrations and genome changes (polyploidy) in the bone marrow cells of mice early and 3 months after the injection. The quantity of early precursors of erythropoiesis in the bone marrow decreased, as did their proliferative potential irrespective of the animal gender. Injection of paclitaxel in the MTD caused the development of bone marrow hypoplasia during the early period of observation (up to 14 days) and 3 months after injection.
Aim of the study was to investigate the possible mutagenic properties of a new drug based on a lithium-containing substance – a complex of lithium citrate, polymethylsiloxane and aluminum oxide. Material and methods. Methods for testing mutagenicity using chromosomal aberrations in the bone marrow cells of CBA mice and somatic recombination in Drosophila melanogaster were used. Results. It was shown that a single intragastric administration of drug at a dose of 5000 mg/kg and a fivefold course of administration at a dose of 400 mg/kg to CBA mice did not increase the level of cytogenetic disorders in bone marrow cells. The study of the lithium complex drug in a somatic mosaicism test revealed that the preparation at a dose of 2000 mg/kg does not increase the frequency of mutations in Drosophila melanogaster. Conclusion. A single intragastric administration of the studied drug at a dose of 5000 mg/kg and its course administration (400 mg/kg × 5) do not increase the level of cytogenetic disorders in the bone marrow cells of CBA mice. In the somatic recombination (mosaicism) test system on D. melanogaster, no increase in the appearance of mutant setae and spots on the body and head was observed when using yellow and singed markers. The results of the study indicate that the studied drug does not have mutagenic properties.
The gene protection effects of the hairy transgenic root extract, obtained as a result of the transformation of Scutellaria baicalensis into Agrobacterium rhizogenes, were revealed on a model of paclitaxel induced genotoxicity in mouse bone marrow and the Drosophila melanogaster somatic cells both under acute and chronic administration at the early and late periods of the study. The stimulation of granylocyto- and erythrocytopoiesis was demonstrated for the hairy roots extract of Scutellaria baicalensis on a rat model of paclitaxel- induced myelosuppression.
We studied toxicity of a new Russian radiopharmaceutical Nanocolloid, 99mTc-Al2O3. Tests for acute toxicity showed that this agent belongs to a class of moderate-toxicity substances and does not have cumulative properties. The evaluation of subchronic toxicity after subcutaneous injection of this product to rats (0.04, 0.2, and 0.4 ml/kg) and rabbits (0.02 and 0.2 ml/kg) for 7 days did not reveal changes in the general state, temperature, body weight, indices of the peripheral blood and bone marrow, functions of the heart, liver, kidneys, and nervous system, and morphological characteristics of the internal organs in animals. The drug does not produce a local irritant effect.
Intramuscular injections of Relatox in therapeutic and toxic doses to young outbred laboratory rats for 14 days caused no changes in the peripheral blood and bone marrow parameters, serum biochemical parameters, and morphology of the major viscera. In the toxic dose, the drug caused local irritation (inflammation, atrophy, and sclerosis in muscle tissue). Regeneration processes started in muscle tissue 7 days after Relatox withdrawal.
Gene protective properties of synthetic antioxidant thiophane and the extract of in vitro cultivated roots of Scutellaria baicalensis were studied on the model of Dr. melanogaster larvae genetic structure damage by drugs cisplatin and cyclophosphan (cyclophosphamide). It is established that adding thiophane or Scutellaria baicalensis root extract to a nutrient medium leads to a decrease in amount of Dr. melanogaster recombinants (females bearing recessive yellow and/or singed marker mutations).
Background. Toxic testing of new pharmacological substances is an obligatory part of preclinical drug development. Nowadays RIPRM named E.D. Goldberg study a medicine based α(1,2)-L-рамно-α(1,4)-D-галактопиранозилуронана from rhizomes Acorus calamus L. Methods. Somatic mosaicism were tested in Drosophila melanogaster. Mutant bristles of heterozygous female of first generation phenotype singed were counted as well spots and bristles on the bodies of phenotype yellow after breeding them in the environment with adding of the studied medicine, concentration 4 and 6.25 %. Results. Authentic differences were not detected in experimental groups in females compared with control groups. Conclusions. A(1,2)-L-ramno-a(1,4)-D-galactopiranoziluronan Acorus calamus L. does not display mutagenic characteristics
The effect of root extract of Baikal skullcap (Scutellaria baicalensis) cultivated in vitro, on the gene structure of CBA/CaLac mice bone marrow cells damaged by anticancer drugs paclitaxel and cisplatin has been studied. It is established that the root extract exhibits gene protective property upon both single and chronic administration.
The effect of root extract of Baikal skullcap ( Scutellaria baicalensis ) cultivated in vitro , on the gene structure of CBA/CaLac mice bone marrow cells damaged by anticancer drugs paclitaxel and cisplatin has been studied. It is established that the root extract exhibits gene protective property upon both single and chronic administration.
Beginning with the first hours of experiments, cisplatin evoked an increase of chromosomal aberrations in CBA/CaLac bone marrow cells. Significant increase of structural infringements of chromosomes due to chromatid breaks was revealed in metaphase plates of murine bone marrow preparations through 24 h after cisplatin intraperitoneal introduction. In late terms of research (90th day), the high level of aberrations of chromosomes was retained. The most pronounced correction of cisplatin mutagenicity was achieved using a preliminary course of thiophan introduction.