Endogenous Repair System of Oxidative Damage of DNA

2019 ◽  
Vol 13 (2) ◽  
pp. 110-119 ◽  
Author(s):  
Anmol Sharma ◽  
Pawan Gupta ◽  
Pranav Kumar Prabhakar

DNA is one of the most important biomolecules of living cells which carries genetic information from generation to generation. Many endogenous and exogenous agents may disrupt the structure of DNA. Change in the cellular genome can lead to errors in replication, transcription and in protein synthesis. DNA damage occurs naturally or result from a metabolic and hydrolytic process which release some very active chemical entities like free radicals, Reactive Oxygen Species (ROS), Reactive Nitrogen Intermediate (RNI), Reactive Carbonyl Species (RCS), lipid peroxidation products and alkylating agents. Superoxide radical, hydroxyl radical and hydrogen peroxide cause a significant threat to cellular integrity by damaging the DNA, lipids, proteins and other biomolecules. Oxidative stress may be explained as a disturbance in the number of free radicals and our system’s ability to neutralize these free radicals. Imbalances in the normal redox potential can also lead to toxic effects via the generation of peroxides. Oxidation of DNA bases leads to the base damage, nick in the strand and break in the strand either single or double strand. Oxidative stress can also cause modifications in normal mechanisms of cell signaling. DNA mutation can result in a number of genetic abnormalities such as cancer, heart failure, Alzheimer’s disease, and depression. Human body has special protection in the form of antioxidant molecules and enzymes against these free radicals. Generation of ROS and its neutralization must be regulated to protect cells and signalling biomolecules from the deleterious effect of oxidative stress with the involvement of antioxidant systems, enzymes, and specific proteins. DNA repair system is a complex system which helps in the identification, removal of the wrong nucleotide and repairs them and as a result, the cell will produce correct and functional protein and active enzyme.

Author(s):  
Fasna K. A. ◽  
Geetha N. ◽  
Jean Maliekkal

Background: Ageing is characterized by a gradual decline in body functions and decreased ability to maintain homeostasis. The free radical theory of ageing proposed by Harman D states that ageing is a result of cumulative damage incurred by free radical reactions. Free radicals are highly reactive molecular species with unpaired electrons; generated in the body by several physiological processes. Prime target to free radical attack are the polyunsaturated fatty acids of cell membranes causing lipid peroxidation. The free radicals are neutralized by the exogenous and endogenous antioxidant systems. Oxidative stress occurs when large number of free radicals are produced or the antioxidant activity is impaired. The present study is focused to find out the role of oxidative stress in ageing.Methods: A cross sectional observational study was undertaken to assess the oxidative stress in ageing; by determining the levels of lipid peroxidation product- malondialdehyde (MDA), the antioxidants- superoxide dismutase (SOD) and ceruloplasmin in various age groups. 150 healthy subjects were selected randomly and categorised into three different age groups of 20-30 years, 40-59 years and 60-90 years; with 50 subjects in each group. Results were expressed as mean ± standard deviation.Results: a significant elevation in serum MDA level and a decline in SOD were observed in 40-59 years and 60-90 years age groups. However, an elevated ceruloplasmin level was found in the above age groups.Conclusions: Aforementioned observations are suggestive of an association between oxidative stress and the progression of ageing process.


1999 ◽  
Vol 7 (1) ◽  
pp. 31-51 ◽  
Author(s):  
Klara D Vichnevetskaia ◽  
D N Roy

Increased levels of active oxygen species or free radicals can create an oxidative stress. Concentration of free radicals in living cells increases as a result of exposure to environmental stresses that lead to aging, carcinogenesis, and immunodeficiencies in animals, and membrane leakage, senescence, chlorophyll destruction, and decreased photosynthesis in plants. The antioxidative system of higher plants consists of enzymes, low molecular weight compounds (among them peptides, vitamins, flavonoids, phenolic acids, alkaloids, etc.), and integrated detoxification chains. Enzymatic defense in plants include enzymes capable of removing, neutralizing, or scavenging oxy-intermediates. Catalases and superoxide dismutases are the most efficient antioxidant enzymes. Free radicals cause cell damage by a lipid peroxidation mechanism, which results in a blockade of natural antioxidant systems. Application of synthetic antioxidants can assist in coping with oxidative stress. There are very few publications on effects of synthetic antioxidants on plant growth and physiology. One of the examples of such synthetic antioxidant is 2-methyl-4-dimethylaminomethyl-5-hydroxybenzimidazole (Ambiol), which substantially promoted growth of agricultural and forestry plant species. Ambiol also demonstrated antitranspirant properties, increasing drought tolerance of conifers and agricultural species. The response of plants to Ambiol is under high genetic control. The identification of genes responsible for the reaction of plants to Ambiol may lead to attempts in genetic engineering of organisms with increased tolerance to oxidative stress. It seems impossible to find a universal scavenger trapping all free radicals active in the organism. However, analysis of the structure–activity relationships in antioxidants can contribute to the search for effective antioxidants.Key words: oxidative stress, lipid peroxidation, free radicals, natural and synthetic antioxidants, Ambiol.


Author(s):  
Georgina Crespo ◽  
Luis Alejandro Di Toro ◽  
Valbuena Desiree ◽  
Jose Luis Perez Vicuña ◽  
María Paula Díaz ◽  
...  

Cancer development is a product of cellular growth and proliferation caused by DNA mutations, nevertheless, other processes are able to favor tumoral progression, such as the activity of reactive oxygen species (ROS) produced within cells as a result of different metabolic reactions. Oxidative stress is defined as an imbalance between free radicals and highly reactive metabolites synthesis and the antioxidant system capacity to eliminate these molecules. In this sense, the overproduction of free radicals is a typical feature of neoplastic cells that allows the promotion of cellular processes related to survival, proliferation, invasion, and metastasis. Furthermore, underlying mechanisms involved in malignant transformation can modify the antioxidant systems in charge of ROS elimination. However, cancer has the particularity of presenting a dual behavior in which both antioxidant or prooxidant activity within tumoral cells can predominate depending on the stage of the disease. As a consequence, many therapeutic efforts have been directed into the stimulation or inhibition of oxidant and antioxidant components in the tumor microenvironment. The aim of this review is to describe the role of oxidative stress in cancer biology and its therapeutic potential.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sonia Gandhi ◽  
Andrey Y. Abramov

Biological tissues require oxygen to meet their energetic demands. However, the consumption of oxygen also results in the generation of free radicals that may have damaging effects on cells. The brain is particularly vulnerable to the effects of reactive oxygen species due to its high demand for oxygen, and its abundance of highly peroxidisable substrates. Oxidative stress is caused by an imbalance in the redox state of the cell, either by overproduction of reactive oxygen species, or by dysfunction of the antioxidant systems. Oxidative stress has been detected in a range of neurodegenerative disease, and emerging evidence from in vitro and in vivo disease models suggests that oxidative stress may play a role in disease pathogenesis. However, the promise of antioxidants as novel therapies for neurodegenerative diseases has not been borne out in clinical studies. In this review, we critically assess the hypothesis that oxidative stress is a crucial player in common neurodegenerative disease and discuss the source of free radicals in such diseases. Furthermore, we examine the issues surrounding the failure to translate this hypothesis into an effective clinical treatment.


Author(s):  
Anastasia Rybakova ◽  
Nadezhda Platonova ◽  
Ekaterina Troshina

A large number of socially significant diseases is accompanied with oxidative stress and carry with tissue damage. Free radicals play a crucial role in the development of these diseases. Similar processes occur under the influence of ionizing radiation and bacterial infections. Recently, was indicated the significant role of oxidative stress in the development of autoimmune thyroiditis. It is assumed that the synthesis of thyroid hormones depends on the concentration of H2O2, which, due to its high toxicity, must be in strict accordance with the activity of antioxidant systems. Many biochemically negative processes occur on the apical membrane of the thyrocyte, which allows limiting the effect of free radicals and avoid cell destruction. However, in pathological conditions, enzymatic systems are disturbed and their components become abnormally activated in the cytoplasm, and it is leads to functional and morphological disorders. A deeper understanding of oxidative stress and its role in the development of autoimmune thyroiditis can contribute to the identification of new methods for its assessment, the expansion of therapeutic ranges for this disease. This review discusses oxidative stress, which is the accumulation of active damaging agents (free radicals, prooxidants, reactive oxygen species) that initiate cell damage and lead to the development of various pathological conditions.


Author(s):  
Robert Peter Biney ◽  
Thabisile Mpofana ◽  
Ella Anle Kasanga

Free radicals are intricately woven into the fabric of oxidative stress and are significant in the development of neurodegenerative disorders (NDs). This chapter examines free radicals in the context of neurodegeneration and provides overview of the multiple roles they play in the pathophysiology and clinical progression of varying NDs including Pick's disease (PiD), Parkinson's disease (PD), Alzheimer's disease (AD), prion diseases (PrD), traumatic brain injury, and aging. The molecular mechanisms of degeneration in Huntington's disease (HD) are also examined with respect to free radicals. Different antioxidant systems and their mechanisms of action are briefly reviewed in addition to the role of diet in aging. The effectiveness of selected synthetic drugs and natural products used in oxidative stress is also reviewed. Lastly, the chapter examines challenges associated with the use of antioxidants and how promising future directions like the endocannabinoid system is being pursued in the race to effectively manage NDs.


2014 ◽  
Vol 31 (4) ◽  
pp. 207-217 ◽  
Author(s):  
Dragana Stojiljković ◽  
Dušica Pavlović ◽  
Ivana Arsić

Summary Skin aging is a dynamic process that occurs due to chronological and photo-aging caused by the influence of external factors, especially ultraviolet-UV radiation. Cumulative oxidative stress, formation of free radicals and their adverse effects on biological systems in the skin cells is a common mechanism of both skin aging processes. The formed reactive oxygen species-ROS can lead to the oxidation of cell`s building molecules. Lipid peroxidation, membrane protein damage and DNA mutation may lead to many structural, functional and aesthetic changes in the skin and can also initiate development of many diseases. One of the skin defense mechanisms is antioxidant defense where enzymes and other antioxidant substances react directly with ROS, preventing them from reaching their biological target. Antioxidant substances have the ability to bind free radicals, caused by oxidative stress, and may have significance in prevention and/or therapy of various skin diseases, as well as in slowing the skin aging process. Topical application of antioxidants, such as vitamin C and E, coenzyme Q10 and polyphenolic compounds may provide the strengthening of the skin endogenous protection system and protection from harmful effects of ROS and oxidative damage to the skin. This article outlines the impact of oxidative stress on the chronological and photo- aging, its mechanism of action, the changes that occur on/in the skin during the aging process. Substances with antioxidant characteristics, which can be used in the prevention of chronological and/or treatment of photo-aging of the skin are shown.


2019 ◽  
Vol 2019 ◽  
pp. 1-29 ◽  
Author(s):  
Meghri Katerji ◽  
Maria Filippova ◽  
Penelope Duerksen-Hughes

Reactive oxygen species (ROS) are common by-products of normal aerobic cellular metabolism and play important physiological roles in intracellular cell signaling and homeostasis. The human body is equipped with antioxidant systems to regulate the levels of these free radicals and maintain proper physiological function. However, a condition known as oxidative stress (OS) occurs, when ROS overwhelm the body’s ability to readily detoxify them. Excessive amounts of free radicals generated under OS conditions cause oxidative damage to proteins, lipids, and nucleic acids, severely compromising cell health and contributing to disease development, including cancer. Biomarkers of OS can therefore be exploited as important tools in the assessment of disease status in humans. In the present review, we discuss different approaches used for the evaluation of OS in clinical samples. The described methods are limited in their ability to reflect on OS only partially, revealing the need of more integrative approaches examining both pro- and antioxidant reactions with higher sensitivity to physiological/pathological alternations. We also provide an overview of recent findings of OS in patients with different types of cancer. Identification of OS biomarkers in clinical samples of cancer patients and defining their roles in carcinogenesis hold great promise in promoting the development of targeted therapeutic approaches and diagnostic strategies assessing disease status. However, considerable data variability across laboratories makes it difficult to draw general conclusions on the significance of these OS biomarkers. To our knowledge, no adequate comparison has yet been performed between different biomarkers and the methodologies used to measure them, making it difficult to conduct a meta-analysis of findings from different groups. A critical evaluation and adaptation of proposed methodologies available in the literature should therefore be undertaken, to enable the investigators to choose the most suitable procedure for each chosen biomarker.


2021 ◽  
Vol 2 (3) ◽  
pp. 67-74
Author(s):  
Vladimir V. Borisov ◽  

Oxidative stress (OS) results from imbalance between the inherent production of reactive oxygen species (ROS) and the capture of ROS by natural antioxidants in the living organism, as well as from failure of antioxidant systems involving cells’ exposure to excess levels of ROC, molecular oxygen or its active forms (free radicals). Pathologic conditions result in imbalance between the quantity of ROC and free radicals produced, and the possibilities of their utilization. Consequently, free radicals, that the antioxidant systems have been unable to neutralize, damage cell structures (membranes, mitochondria, DNA, etc.). These processes occur both in germ cells (sperm, oocytes), and spermoplasm. In fact, a number of recent studies have confirmed that COVID-19 is a gender-related disorder: most patients with severe infection are males. Studying the viral entry mechanism has revealed that it may cause the profound damage to cells of reproductive system, and lead to delayed reproductive function impairment in young men and adolescents. Vitamin and mineral supplementation with optimum proportion of ingredients may be used as an efficient reinforcement for therapy aimed at fertility preservation and restoration in the current context of the pandemic.


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