The review summarizes literature data on the DNA-binding, DNA-protecting and DNA-damaging activities of a range of natural human endogenous and exogenous compounds. Small natural organic molecules ...bind DNA in a site-specific mode, by arranging tight touch with the structure of the major and minor grooves, as well as individual bases in the local duplex DNA. Polyphenols are the best-studied exogenous compounds from this point of view. Many of them demonstrate hormetic effects, producing both beneficial and damaging effects. An attempt to establish the dependence of DNA damage or DNA protection on the concentration of the compound turned out to be successful for some polyphenols, daidzein, genistein and resveratrol, which were DNA protecting in low concentrations and DNA damaging in high concentrations. There was no evident dependence on concentration for quercetin and kaempferol. Probably, the DNA-protecting effect is associated with the affinity to DNA. Caffeine and theophylline are DNA binders; at the same time, they favor DNA repair. Although most alkaloids damage DNA, berberine can protect DNA against damage. Among the endogenous compounds, hormones belonging to the amine class, thyroid and steroid hormones appear to bind DNA and produce some DNA damage. Thus, natural compounds continue to reveal beneficial or adverse effects on genome integrity and provide a promising source of therapeutic activities.
•Numerous polyphenols and other natural compounds bind DNA in vitro.•Small organic molecules that bind to DNA can both exogenous and endogenous.•The DNA binding compound can damage and protect DNA against other genotoxic agents.•Conditions, when a compound damages or protects DNA are difficult to elucidate.
Diabetes, a chronic group of medical disorders characterized byhyperglycemia, has become a global pandemic. Some hormones may influence the course and outcome of diabetes, especially if they ...potentiate the formation of reactive oxygen species (ROS). There is a close relationship between thyroid disorders and diabetes. The main objective of this investigation was to find out whether peripheral blood mononuclear cells (PBMCs) are more prone to DNA damage by triiodothyronine (T3) (0.1, 1 and 10 μM) at various stages of progression through diabetes (obese, prediabetics, and type 2 diabetes mellitus—T2DM persons). In addition, some biochemical parameters of oxidative stress (catalase-CAT, thiobarbituric acid reactive substances—TBARS) and lactate dehydrogenase (LDH) were evaluated. PBMCs from prediabetic and diabetic patients exhibited increased sensitivity for T3 regarding elevated level of DNA damage, inhibition of catalase, and increase of TBARS and LDH. PBMCs from obese patients reacted in the same manner, except for DNA damage. The results of this study should contribute to a better understanding of the role of thyroid hormones in the progression of T2DM.
Abstract Systemic oxidative stress stemming from increased free radical production and reduced antioxidant capacity are common characteristics of obese individuals. Using hydrogen peroxide (H2O2) to ...induce DNA damage in vitro, in peripheral blood mononuclear cells (PBMCs) from obese subjects and controls, the DNA protective ability of dihidroqercetin (DHQ) and biochaga (B) alone or in combination, were evaluated. The effects of DHQ and B were estimated under two experimental conditions: pre-treatment, where cells were pre-incubated with the substances prior to H2O2 exposure; and post-treatment when cells were first exposed to H2 H2O2, and further treated with the compounds. DNA damage was evaluated using the comet assay. The results of pre- and post-treatment showed a significant decrease in DNA damage produced by H2O2 in the obese group. This decrease was not significant in control group probably due to a small number of subjects in this pilot study. More prominent attenuation was noted in the pre-treatment with DHQ (250 μg/ml). Analysis of antioxidant properties revealed that DHQ’s remarkable reducing power, 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity, and potent∙OH scavenging properties may contribute to strong attenuation of H2O2-induced DNA damage. Also, B showed strong reducing power, DPPH, and ∙OH scavenging ability, while reducing power and DPPH scavenger effects were increased in the presence of DHQ. Conclusively, DHQ and B may reduce H2O2-induced DNA damage in PBMCs from obese subjects when challenged in vitro, and could be valuable tools in future research against oxidative damage-related conditions.
Thymol is a natural essential oil derived from the plant
L. It is known to be beneficial for human and animal health and has been used in beekeeping practice against
mite for years. In this study, ...the genotoxic and antigenotoxic potential of thymol were evaluated on the honey bee (
L.) continuous cell line AmE-711 for the first time. Using the Comet assay, three increasing concentrations (10, 100, and 1000 µg/mL) of thymol were tested. Negative control (non-treated cells) and positive control (cells treated with 100 µM H
O
) were also included. The absence of thymol cytotoxicity was confirmed with the Trypan blue exclusion test. Thymol in the concentration of 10 µg/mL did not increase DNA damage in AmE-711 honey bee cells, while 100 and 1000 µg/mL concentrations showed genotoxic effects. For testing the antigenotoxic effect, all concentrations of thymol were mixed and incubated with H
O
. The antigenotoxic effect against was absent at all concentrations (10, 100, 1000 μg/mL) tested. Moreover, thymol enhanced the H
O
-induced DNA migration in the Comet assay. The obtained results indicate genotoxic effects of thymol on cultured honey bee cells suggesting its careful application in beekeeping practice to avoid possible negative effects on honey bees.
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•Adrenaline induced DNA damage at conc. of 10 μM in all groups of subjects.•1 μM of adrenaline did not induce DNA damage only in healthy controls.•Adrenaline increased oxidative ...stress and membrane damage in prediabetics and T2DM.
Diabetes represents one of the major health concerns, especially in developed countries. Some hormones such as the stress hormone adrenaline can induce reactive oxygen species (ROS) and may worsen the diabetes. Therefore, the main aim of the investigation was to find out whether peripheral blood mononuclear cells (PBMCs) from normal persons have less DNA damage induced by adrenaline (0.1, 1 and 10 μM) in comparison to PBMCs from obese, prediabetic and diabetic patients. Also, the biochemical parameters of oxidative stress (TBARS, catalase) and lactate dehydrogenase were monitored. It was observed that higher concentrations of adrenaline (1 and 10 μM) induced DNA damage in the obese, prediabetic and diabetic groups. In healthy individuals only the highest concentration of adrenaline caused significant increase in the DNA damage. In summary, total comet score (TCS) comparison has shown significant differences between groups, and DNA damaging effects of adrenaline were most evident in diabetic patients. The results of the biochemical analysis also demonstrate that adrenaline exerts most obvious effects in diabetic individuals which is manifested as significant change of parameters of oxidative stress. In summary, the obtained results demonstrated that diabetics are more sensitive to genotoxic effects of adrenaline and this effect probably resulted from decreased antioxidative defence mechanisms in various stages of progression through diabetes. Therefore, these results could contribute to a better understanding of a role of endocrine factors to damage of cellular biomolecules which could be useful in finding novel therapeutic approaches and lifestyle changes with an aim to lower the possibility of diabetes complications.
•Protective effect of commercial dry olive leaf extract against adrenaline induced DNA damage was tested using comet assay.•Two different experimental protocols were employed, pretreatment and ...post-treatment.•The antigenotoxic and antioxidant properties of dry olive leaf extract are indicated.•The genoprotective effect of the extract is concentration-dependant.•Several mechanisms contributing to its protective action are proposed.
Excessive release of stress hormone adrenaline is accompanied by generation of reactive oxygen species which may cause disruption of DNA integrity leading to cancer and age-related disorders. Phenolic-rich plant product dry olive leaf extract (DOLE) is known to modulate effects of various oxidants in human cells. The aim was to evaluate the effect of commercial DOLE against adrenaline induced DNA damage in human leukocytes by using comet assay. Peripheral blood leukocytes from 6 healthy subjects were treated in vitro with three final concentrations of DOLE (0.125, 0.5, and 1mg/mL) for 30min at 37°C under two different protocols, pretreatment and post-treatment. Protective effect of DOLE was assessed from its ability to attenuate formation of DNA lesions induced by adrenaline. Compared to cells exposed only to adrenaline, DOLE displayed significant reduction (P<0.001) of DNA damage at all three concentrations and under both experimental protocols. Pearson correlation analysis revealed a significant positive association between DOLE concentration and leukocytes DNA damage (P<0.05). Antigenotoxic effect of the extract was more pronounced at smaller concentrations. Post-treatment with 0.125mg/mL DOLE was the most effective against adrenaline genotoxicity. Results indicate genoprotective and antioxidant properties in dry olive leaf extract, strongly supporting further explorations of its underlying mechanisms of action.
This study is aimed at analysing biochemical and genetic endpoints of toxic effects after administration of adrenaline. For this purpose, the study was carried out on Wistar rats and three doses of ...adrenaline were used: 0.75 mg/kg, 1.5 mg/kg, and 3 mg/kg body weight. To achieve these aims, we investigated the effects of adrenaline on catalase (CAT), Cu, Zn-superoxide dismutase (SOD), malondialdehyde (MDA), nitrite (NO2−), carbonyl groups (PCC), and nitrotyrosine (3-NT). Total activity of lactate dehydrogenase (LDH), its relative distribution (LDH1–LDH5) activity, level of acute phase proteins (APPs), and genotoxic effect were also evaluated. The obtained results revealed that all doses of adrenaline induced a significant rise in CAT activity, MDA level, PCC, NO2−, and 3-NT and a significant decrease in SOD activity compared to control. Adrenaline exerted an increase in total activity of LDH, LDH1, and LDH2 isoenzymes. Further study showed that adrenaline significantly decreased serum albumin level and albumin-globulin ratio, while the level of APPs (α1-acid glycoprotein and haptoglobulin) is increased. The micronucleus test revealed a genotoxic effect of adrenaline at higher concentrations (1.5 mg/kg and 3 mg/kg body weight) compared to untreated rats. It can be concluded that adrenaline exerts oxidative and nitrative stress in rats, increased damage to lipids and proteins, and damage of cardiomyocytes and cytogenetic damage. Obtained results may contribute to better understanding of the toxicity of adrenaline with aims to preventing its harmful effects.
Harmful effects of elevated levels of catecholamines are mediated by various mechanisms, including gene transcription and formation of oxidation products. The aim of this study was to see whether the ...molecular mechanisms underlying the damaging action of adrenaline on DNA are mediated by reactive oxygen species (ROS). To do that, we exposed human whole blood cells to 10 μmol L
adrenaline or 50 μmol L
(used as positive control) that were separately pre-treated or post-treated with 500 μmol L
of quercetin, a scavenger of free radicals. Quercetin significantly reduced DNA damage in both pre- and post-treatment protocols, which suggests that adrenaline mainly acts via the production of ROS. This mechanism is also supported by gradual lowering of adrenaline and H
-induced DNA damage 15, 30, 45, and 60 min after treatment. Our results clearly show that DNA repair mechanisms are rather effective against ROS-mediated DNA damage induced by adrenaline.
•Adrenalin has not caused cytogenetic changes in SCE and micronucleus tests.•There was a dose-dependent increase of DNA damage caused by adrenaline.•Quercetin or catalase significantly reduced DNA ...damaging effects of adrenaline.
Catechol groups can be involved in redox cycling accompanied by generation of reactive oxygen species (ROS) which may lead to oxidative damage of cellular macromolecules including DNA. The objective of this investigation was to evaluate possible genotoxic effects of a natural catecholamine adrenaline in cultured human lymphocytes using cytogenetic (sister chromatid exchange and micronuclei) and the single cell gel electrophoresis (Comet) assay. In cytogenetic tests, six experimental concentrations of adrenaline were used in a range from 0.01–500μM. There were no indications of genotoxic effects of adrenaline in sister chromatid exchange and micronucleus tests. However, at four highest concentrations of adrenaline (5μM, 50μM, 150μM and 300μM) we observed a decreased mitotic index and cell-cycle delay. In addition, in the Comet assay we used adrenaline in a range from 0.0005–500μM, at two treatment times: 15min or 60min. In contrast to cytogenetic analysis, there was a dose-dependent increase of DNA damage detected in the Comet assay. These effects were significantly reduced by concomitant treatment with quercetin or catalase. Therefore, the obtained results indicate that adrenaline may exhibit genotoxic effects in cultured human lymphocytes, most likely due to production of reactive oxygen species.
The thyroid hormones change the rate of basal metabolism, modulating the consumption of oxygen and causing production of reactive oxygen species, which leads to the development of oxidative stress ...and DNA strand breaks. Olive (Olea europaea L.) leaf contains many potentially bioactive compounds, making it one of the most potent natural antioxidants. The objective of this study was to evaluate the genotoxicity of L-thyroxine and to investigate antioxidative and antigenotoxic potential of the standardized oleuropein-rich dry olive leaf extract (DOLE) against hydrogen peroxide and L-thyroxine-induced DNA damage in human peripheral blood leukocytes by using the comet assay. Various concentrations of the extract were tested with both DNA damage inducers, under two different experimental conditions, pretreatment and posttreatment. Results indicate that L-thyroxine exhibited genotoxic effect and that DOLE displayed protective effect against thyroxine-induced genotoxicity. The number of cells with DNA damage, was significantly reduced, in both pretreated and posttreated samples (P < 0.05). Comparing the beneficial effect of all tested concentrations of DOLE, in both experimental protocols, it appears that extract was more effective in reducing DNA damage in the pretreatment, exhibiting protective role against L-thyroxine effect. This feature of DOLE can be explained by its capacity to act as potent free radical scavenger.
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