China
Africa
Explore chapters and articles related to this topic
Mitochondrial Genome Damage, Dysfunction and Repair
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Kalyan Mahapatra, Sayanti De, Sujit Roy
The sophisticated antioxidant system of mitochondrial matrix restricts the steady-state concentration of O2‒• within 10–10 M (Cadenas and Davies, 2000). The free radicals escaping from this detoxification process can cause oxidative damage to various biological components. But because mitochondrial DNA is in close proximity to the mitochondrial respiratory chain, it is very much susceptible to oxidative damage by various free radicals. The high rate of oxidative stress operating within the mitochondrial matrix causes a broad spectrum of mitochondrial DNA damage including modifications to bases such as 8-oxo-2′-deoxyguanosine (8-oxodG), 8,5′-cyclo-2′deoxynucleosides, thymine glycol, 5,6-dihydroxycytosine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine. Along with this sugar break down products (such as 2-deoxypentose-4-ulose, 2-deoxypentonic acid lactones and erythrose), base free sites or abasic sites, strand breaks and chemical adducts of bases such as aldehyde modifications are also the consequences of the oxidative stress.
Anti-Aging Drug Discovery in Experimental Gerontological Studies
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Alexander N. Khokhlov, Alexander A. Klebanov, Galina V. Morgunova
If a test compound has a positive effect on the proliferative activity of cells (which is manifested, e.g., in increasing their CFE), the effects of this drug on the organism can be dual type. On the one hand, for some cells (e.g., those involved in the regeneration processes), such stimulation can be useful. On the other hand, this effect can, firstly, stimulate the proliferation of those cells that, as mentioned above, should not divide, and secondly, increase the probability of rapid propagation of the precancerous (or even cancerous) cells present in the organism. An increase in the incidence of benign tumors also cannot be ruled out. However, it should be emphasized that the evaluation of the CFE of cells is one of the few methods that provides data on the characteristics of individual cells rather than the cell population in general (Khokhlov et al. 1991). In the latter case, information about the possible subpopulations of cells that may differently respond to the test compound is lost due to averaging. For example, under the influence of a test factor, the content of 8-oxo-2′-deoxyguanosine, a popular aging biomarker (Esipov et al. 2008), in DNA of different cells may increase, decrease, or remain unchanged. As a result, the estimation of the content of 8-oxo-2′-deoxyguanosine on average can lead to the conclusion about the absence of changes in this parameter.
Vitamin C in Neurological Function and Neurodegenerative Disease
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Shilpy Dixit, David C. Consoli, Krista C. Paffenroth, Jordyn M. Wilcox, Fiona E. Harrison
There is substantial evidence documenting increased oxidative stress in HD, although whether redox imbalance itself contributes to disease progression or is the result of other pathologic mechanisms is debated [156,157]. Several studies analyzing postmortem HD patient brain tissue show increased oxidative stress compared to age-matched controls. Positive markers of oxidative damage to protein, DNA, and lipids, as well as induction of antioxidant defense mechanisms, have been identified in the striatum and regions of cortex [158–161]. However, increased oxidative damage in postmortem HD patient brains is not universally reported [162]. Discrepancies between findings may partially be explained by the challenges of postmortem sample analyses. Confounds such as manner of death, time or season of death, intervening medications, length of postmortem interval prior to analysis, and subject-to-subject variation can all substantially influence the outcome of biochemical assays on postmortem tissue [163]. Although these variables are usually addressed in studies, they do not always contribute to the interpretation of results [164,165]. HD patients also tend to exhibit elevated levels of oxidative stress in peripheral tissues, including blood. Increases in lipid peroxidation and malondialdehyde (MDA), 8-oxo-2′-deoxyguanosine (8-OHdG), carbonylated proteins, as well as decreased levels of reduced glutathione (GSH) and diminished efficiency of antioxidant defense mechanisms have been reported in the blood and leukocytes of HD patients [166–169]. Some of these markers, such as 8-OHdG, even correlate with the severity of disease and may be useful biomarkers for disease progression [167].
Review of mechanisms of genotoxic action of dibenzo[def,p]chrysene (formerly dibenzo[a,l]pyrene)
Published in Toxin Reviews, 2023
K. Kowalczyk, J. Roszak, Z. Sobańska, M. Stępnik
Adult Muta™Mouse males were exposed by oral gavage to DBC at 0, 2, 6.2, or 20 mg DBC/kg bw/d, for 3 d (Chepelev et al.2016). A dose-dependent increase in the levels of DBC–DNA adducts after exposure to all doses and at all time points was observed in the spleen and bone marrow. The main adducts determined were from DBC-11,12-diol-13,14-epoxide. In the spleen, about 2-fold higher levels of the adducts were measured than in the bone marrow. A decrease in the adduct levels in the bone marrow was observed from 4 to 72 h. In contrast, in the spleen there was over a 2-fold increase in adduct levels from 4 to 24 h at the highest dose. DNA oxidation in the spleen quantified as dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dG) increased only at the highest dose and only at the 4 h post-exposure time-point (1.9-fold increase vs. control).
Changes in health-related outcomes among colorectal cancer patients undergoing inpatient rehabilitation therapy: a systematic review of observational and interventional studies
Published in Acta Oncologica, 2021
Sophie Scherer, Lina Jansen, Daniel Boakye, Michael Hoffmeister, Hermann Brenner
Results from two studies suggest that the intensity of endurance training during rehabilitative treatment could influence immune response [41] and the level of oxidative stress [42]. Both studies compared 2-week aerobic exercise with lower (30–40% × maximal exercise capacity) and higher intensity (50–60%/55–65%). A significant reduction in oxidative stress levels measured by urinary 8-Oxo-2′-deoxyguanosine was observed from before treatment to after treatment in the lower exercise intensity group in comparison to no significant reduction in the higher-intensity group [42]. A significant decrease in anti-inflammatory cytokines (Lipopolysaccharide-stimulated interleukin-1 receptor antagonist) was observed in the higher-intensity group in comparison to no significant change in the lower-intensity group [41]. The potential benefit for both outcomes, with respect to infection rate, anti-tumor response, and survival, is unknown hitherto as pointed out by the authors.
Polystyrene nanoparticles: the mechanism of their genotoxicity in human peripheral blood mononuclear cells
Published in Nanotoxicology, 2022
Kinga Malinowska, Bożena Bukowska, Ireneusz Piwoński, Marek Foksiński, Aneta Kisielewska, Ewelina Zarakowska, Daniel Gackowski, Paulina Sicińska
The most important DNA oxidation biomarkers are oxidized products of guanine and deoxyguanosine, which include 8-oxo-2′-deoxyguanosine (8-oxodG). To detect 8-oxodG, PBMCs were exposed to PS-NPs in concentration range from 0.0001 to 100 µg/mL for 24 h. The cells were subsequently frozen. In the next stage, DNA isolation was performed, as described in the Section 2.1.2, and the tested parameter was determined in the obtained DNA isolates. Two-dimensional (2D) liquid chromatography was used for the 8-oxodG analysis. Changes in the tested parameter were observed only after PBMCs exposure to the smallest size NPs. A statistically significant increase in 8-oxodG occurred from their concentration of 0.1 µg/mL (Figure 10).