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Red beetroot (Beta vulgaris L.) is known as the popular vegetable in Russian cuisine, as well as a plant food that protects human health. Beetroot is rich in chemical compounds with antioxidant, anticarcinogenic, anti-inflammatory and other health-beneficial properties. Using the DNA-comet method (alkaline version), the effect of dry red beetroot extract was assessed as part of a meat product on spontaneous and induced DNA damage and presence of “abnormal comet” indicators in cells of various parts of the gastrointestinal tract (GIT) and liver of male F1 mice C.B.A. x C57 Bl /6. The obtained results showed that intraperitoneal administering of alkylating agent methyl methanesulfonate (MMS) to the mice at a dose of 40 mg/kg of the animal body weight statistically significantly increased the numerical value of DNA damage (% DNA in the tail) and the number of atypical DNA-comet in the liver, stomach, small and large intestines. Introduction of meat product with added red beetroot extract (20 g/kg of finished product) into the diet of the animals did not provide any significant effect on the scope of DNA damage caused by MMS in liver cells, but it led to a statistically significant decrease of this parameter by 58%, 59% and 48% in cells of the stomach, duodenum and rectum, respectively. The significant decrease of 29–54% in the release of atypical DNA-comet in the cells of all organs studied has been also confirmed, which proves decreasing in the cytotoxic effect of MMC in the gastrointestinal tract and liver. Thus, the antigenotoxic and cytoprotective effects of a meat product with addition of dry red beetroot extract have been recorded. This finding is able to have significant practical application, since the complications and issues in the gastrointestinal tract often occur and secondary tumors are induced in its parts during the chemotherapy of cancer located beyond the gastrointestinal tract. This result shows the potential ability of the developed meat product in protecting gastrointestinal tract cells from the genotoxic and cytotoxic effects of alkylating anticancer drugs

Relevance. Diabetes mellitus is a widespread, socially significant disease. In this regard, it is important to obtain an experimental model that precedes subsequent experiments on pharmacological screening and/or study of the mechanism of action of antidiabetic agents.The aim of this work was a comparative assessment of the manifestation of hyperglycemia, DNA damage, and morphology of internal organs in BALB/c mice in the modeling of diabetes mellitus by a single administration of streptozotocin at a dose of 200 mg/kg and its fractional, five-day administration at a rate of 40 mg/kg per day.Methods. Streptozotocin was used as an inducer of diabetes. The drug was administered to mice once at a dose of 200 mg/kg or 5 times daily at a dose of 40 mg/kg. We monitored hyperglycemia, DNA damage in the cells of the brain, liver, kidneys, pancreas and testes, and also assessed the microscopic picture of individual internal organs, including the pancreas.Results. In both variants of the experiment, the reproduction of pathognomonic signs of diabetes mellitus is traced. They are somewhat more clearly seen in the variant of the experiment with a fractional, five-day administration of streptozotocin in single doses of 40 mg/kg.

Genotoxic lesions are not only a cause of genetic pathologies and cancer, but also the most common and significant factor of the etiopathology of cardiovascular and neurodegenerative disorders, reproductive losses, infertility, and aging. This requires careful monitoring of the use of potential genotoxicants including medicinal products (MPs), which are a group of compounds intentionally and routinely used by humans. Genotoxicity assesment is highly essential in preclinical drug safety studies. The aim of the study was to analyse the current situation and reveal possible ways of addressing methodological and regulatory issues in genotoxicology to enable proper conduction of drug safety preclinical studies. The article summarises basic concepts of the modern genetic toxicology development and highlights the history of research aimed at identifying mutagenic, clastogenic, and aneugenic effects. The authors analyse regulatory aspects of genotoxicological studies of MPs and consider issues of improving the strategy for genotoxicity testing. The paper gives information about the genotoxicity tests approved for MPs, recommendations for interchangeability of tests in relation to particular study characteristics. The authors carried out a comparative analysis of the tests’ pros and cons with an emphasis that the study of each MP is a separate scientific task. They discuss interpretation of results and prediction of MP carcinogenic potential in genotoxicological studies. Recommendations are given for the optimisation of the MP genotoxicity assessment strategy, considering its partial integration into general toxicity studies. The article stresses the urgent need to develop registration methods for genotoxic events in germ cells, assesses the prospects of new tests, and reviews new trends in drug genotoxicology fundamental research.

Hemantane (N-adamant-2-yl-hexamethylenimine hydrochloride) is an antiparkinsonian drug with a multicomponent mechanism of action, including a modulating effect on the activity of dopamine and serotonergic mediator systems, a selective inhibitory effect on MAO-B, properties of a low-affinity non-competitive channel blocker of glutamate NMDA receptors, has moderate antiradical and anti-inflammatory activity. The aim of this study was to assess the effect of the neurotoxin MPTP, which is used for modeling of parkinsonian syndrome, and the hemantane on the DNA integrity in the striatum and frontal cortex of the brain of C57BL/6 mice by the DNA comet assay – gel electrophoresis of DNA single cells. Results. In the first experiment, hemantane was administered once a day for 5 days before the MPTP (20 mg/kg, i.p.), then together with MPTP once a day for 5 days. In the second experiment hemantane 10 mg/kg was injected preliminarily for 4 days and 40 minutes before MPTP 30 mg/kg. The obtained results confirm the absence of an effect on DNA of hemantane at a therapeutic dose of 10 mg / kg. In the experimental schemes used, we did not reveal the expected increase in the level of DNA damage under the influence of MPTP, and, accordingly, we were not able to assess the protective effect of hemantane.

Resume. Relevance. Alcoholic cardiomyopathy (ACM) is a specific heart muscle disease found in individuals with a history of long-term heavy alcohol consumption. Their underlying mechanisms are poorly known, leading to a lack of effective therapy. Related with oxidative stress DNA damage and cell death play an essential role in the development of alcoholic cardiomyopathy. The aim of present study - using previously developed translation model to evaluate the levels of DNA damage and apoptosis in the myocardium of rats with ACM and modulating effect of cardioprotective drugs. Methods. ACM was established by forced alcoholization of rats (10 % ethanol solution as the only source of drinking water for 24 weeks; mean daily ethanol consumption was 5.0-6.5 g/kg). Trimetazidine (20 or 30 mg/kg), fabomotizole (15 mg/kg) or their combination (20 + 15 mg/kg) were injected ip, daily during following 4 weeks of abstinence. DNA damage was evaluated using alkaline and neutral comet assay. Apoptosis was assessed by TUNEL assay in paraffin-embedded sections. Results. No DNA damage or apoptosis of the myocardial cells was observed in rats with alcoholic cardiomyopathy at the abstinence period. A decrease in the level of cardiomyocytes with a high degree of DNA fragmentation, referred to as “hedgehog” DNA comets and that are presumably cells at the stage of autophagic fragmentation of chromatin, was revealed. Treatment of rats at the abstinence period with cardioprotective drugs trimetazidine and fabomotizole or their combination raised “hedgehog” DNA comets level up to control value. Conclusion. Our findings allows considering the appearance of cardiomyocytes with highly fragmented DNA as an important mechanism for regulating and maintaining myocardial homeostasis in ACM.

Objective. To study the mechanisms of posttraumatic changes in the blood cells, by investigating DNA damages associat ed with hypoxia caused by massive blood loss (BL) in severe injury.Subjects and methods. Ninetyfive patients aged 40.6±16.5 years (from 20 to 79 years) who had sustained severe mechanical injury with different BL volumes (BLV) (from 100 to 4000 ml) and hemodynamic disorders were examined to study DNA damages and white blood cell necrotic and apop totic processes. In terms of the victims' weight, the mean BL was 21.5±16.5 ml/kg (from 1.4 to 61.5 ml/kg). The victimswere divided into 4 groups according to BLV: 1) 26 victims whose BLV was less than 750 ml (5.93±2.41 ml/kg) (grade I BL); 2) 23 victims whose BLV was 750—1500 ml (11.5±1.5 ml/kg) (grade 2 BL); 3) 23 victims whose BLV was 1500—2000 ml (23.8±4.0 ml/kg) (grade 3 BL); 4) 23 victims whose BLV was over 2000 ml (45.6±10.1 ml/kg) (grade 4 BL), according to the type of injury: 1) severe skeletal injury (SSI) (n=17); 2) brain injury (BI) (n=43); 3) a concurrence of SSI and BI (SSI+BI) (n=35); according to the development of infectious complications: 1) 69 victims who developed infectious com plications on days 5—7 postinjury; 2) 26 victims who did not. To evaluate the impact of hypoxia on DNA damages, white blood cell apoptotic and necrotic processes, the victims were divided into 2 groups: 1) hypoxia (18 of the 95 victims who had 4 altered indicators, such as capillary blood pO2, plasma lactate levels, pH, and BE); 2) no hypoxia (10 of the 95 victims whose indicators were within the normal range). DNA damages and necrotic and apoptotic changes in the white blood cells were assessed by the DNA comet assay. The plasma concentration of extracellular DNA was fluorometrically determined using a QuantiTTM HS DNA Assay Kit (Invitrogen, USA). That of 8hydroxy2deoxyguanosine was estimated by enzyme immunoassay employing an 8hydroxy2deoxyGuanosine EIA Kit (Cayman Chemical, USA). The levels of cas pase3, caspase9, superoxide dismutase, and sAPO1/FAS were measured by enzyme immunoassay using test systems(Bender MedSystems, Austria).Results. There were significantly higher plasma levels of free DNA in the victims than in the controls throughout the followup, which is due to its exit from the cells damaged from tissue injury. In the first two weeks after injury, there were increases in DNA damages and white blood cell alteration processes by a necrotic and apoptotic mechanism in the victims with different types of injury, which may be associated with the active participation of leuko cytes in the processes of cellular breakdown product removal in the tissues damaged during injury and the in those of prevention of infectious complications. In the victims, white blood cell alteration in the necrotic pathway does not depend on BLV and hypoxia degree while that in the apoptotic pathway showed a relationship of leukocyte alteration to hypoxia in these patients. The sum of the values of necrotic DNA comets, apoptotic DNA comets, and single and doublestrand breaks on day 3 postinjury may serve as a predictor of the likely development of infectious complications in victims with injury, blood loss, and marked hypoxia. There were differences in the levels of DNA damages and white blood cell apoptosis and necrosis in the victims with BI and SSI. The injury victims showed a threefold decrease in plasma 8hydroxy2 deoxyguanosine concentrations, which was accompanied and, possibly, caused by an increase in the amount of superoxide dismutase.Conclusion. There was a relationship between the degree of DNA damages, apoptosis, and necrosis in the white blood cells of victims with injury and hypoxiainduced blood loss.

Abstract Study was performed by counting cells with chromosomal aberrations in C57Bl/6 mice. Bark dry extract was given perorally in doses of 50, 150, 450, and 1500 mg/kg. Mutagens dioxidine and cyclophosphamide were injected intraperitoneally in doses of 200 and 20 mg/kg, respectively. Bark dry extract in doses of 150 and 1500 mg/kg did not possess cytogenetic activity. Bark dry extract in doses of 50, 150, and 450 mg/kg significantly decreased the cytogenetic effect of mutagens under various regimens of treatment with the preparation (single combined administration, 5-day pretreatment, and 5-day combined administration). Our results indicate that bark dry extract possesses antimutagenic properties. [ABSTRACT FROM AUTHOR]

The total antioxidant capacity (TEAC assay) of blood plasma from healthy donors was studied before and after 2- and 4-week consumption of the vitamin and mineral complex containing the major antioxidant vitamins and cofactors of antioxidant enzymes. Before the treatment the donors were divided into 2 subgroups with initially high and low total antioxidant capacity. After 2-week course of vitamin and mineral complex the total antioxidant capacity considerably decreased in group 1 donors, but increased in group 2 donors. After 4-week course this index increased in donors of both subgroups and slightly surpassed the baseline level typical of individuals with high total antioxidant capacity. [ABSTRACT FROM AUTHOR]

The study investigated antigenotoxic and antimutagenic activity of novel lignin-derived polyphenolic composition (BP-C2) with ammonium molybdate towards cyclophosphamide and dioxidine in the bone marrow, blood and liver cells of BALB/c mice. BP-C2 was given to mice via gavage at 60, 80 and 120 mg/kg once 1 h before single intraperitoneal injection of a genotoxic agent. 1.5 h and 3 h after dioxidine or cyclophosphamide injection, respectively, cellular suspensions were obtained from mice and assessed with the comet test and cytogenetic analysis of bone marrow cells. It was observed that antigenotoxic activity of BP-C2 against DNA damage induced by dioxidine, a prooxidant genotoxic agent, in the bone marrow, liver and blood cells of mice in vivo was more pronounced at 60 and 80 mg/kg than at 120 mg/kg. When cyclophosphamide was used to induce a DNA damage, the genoprotective effect of BP-C2 was observed in bone marrow, liver and blood cells at 60 mg/kg dose but the effect was not significant at 80 mg/kg. When co-administered with 120 mg/kg BP-C2, cyclophosphamide induced a higher level of DNA damage in liver cells, but its genotoxic effect in bone marrow and blood cells was the same as when it was administered alone. When assessing the effect of BP-C2 on chromosomal aberrations induced by cyclophosphamide and dioxidine in bone marrow cells, it was revealed that all three tested doses of BP-C2 significantly decreased the number of cells with chromosome abnormalities. Thus, BP-C2 has a pronounced antimutagenic and genoprotective effects.