At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

/pdf/free-radicals-in-the-physiological-control-of-cell-function-g3w3iyr0ph.pdf

Free Radicals in the Physiological Control of Cell Function

http://www.biblioteca.uma.es/bbldoc/articulos/16689835.pdf?origin=publication_detail

Antioxidant enzymes and human diseases

A significant amount of reactive oxygen species (ROS) is generated during mitochondrial oxidative phosphorylation. Several studies have suggested that mtDNA may accumulate more oxidative DNA damage relative to nuclear DNA. This study used quantitative PCR to examine the formation and repair of hydrogen peroxide-induced DNA damage in a 16.2-kb mitochondrial fragment and a 17.7-kb fragment flanking the β-globin gene. Simian virus 40-transformed fibroblasts treated with 200 μM hydrogen peroxide for 15 or 60 min exhibited 3-fold more damage to the mitochondrial genome compared with the nuclear fragment. Following a 60-min treatment, damage to the nuclear fragment was completely repaired within 1.5 hr, whereas no DNA repair in the mitochondrion was observed. Mitochondrial function, as assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction, also showed a sharp decline. These cells displayed arrested-cell growth, large increases in p21 protein levels, and morphological changes consistent with apoptosis. In contrast, when hydrogen peroxide treatments were limited to 15 min, mtDNA damage was repaired with similar kinetics as the nuclear fragment, mitochondrial function was restored, and cells resumed division within 12 hr. These results indicate that mtDNA is a critical cellular target for ROS. A model is presented in which chronic ROS exposure, found in several degenerative diseases associated with aging, leads to decreased mitochondrial function, increased mitochondrial-generated ROS, and persistent mitochondrial DNA damage. Thus persistent mitochondrial DNA damage may serve as a useful biomarker for ROS-associated diseases.

https://www.pnas.org/content/pnas/94/2/514.full.pdf

Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress

Lipid hydroperoxide generation, turnover, and effector action in biological systems

Oxidative stress is an unavoidable consequence of life in an oxygen-rich atmosphere. Oxygen radicals and other activated oxygen species are generated as by-products of aerobic metabolism and exposure to various natural and synthetic toxicants. The "Oxygen Paradox" is that oxygen is dangerous to the very life-forms for which it has become an essential component of energy production. The first defense against oxygen toxicity is the sharp gradient of oxygen tension, seen in all mammals, from the environmental level of 20% to a tissue concentration of only 3-4% oxygen. These relatively low tissue levels of oxygen prevent most oxidative damage from ever occurring. Cells, tissues, organs, and organisms utilize multiple layers of antioxidant defenses and damage removal, and replacement or repair systems in order to cope with the remaining stress and damage that oxygen engenders. The enzymes comprising many of these protective systems are inducible under conditions of oxidative stress adaptation, in which the expression of over 40 mammalian genes is upregulated. Mitotic cells have the additional defensive ability of entering a transient growth-arrested state (in the first stages of adaptation) in which DNA is protected by histone proteins, energy is conserved by diminished expression of nonessential genes, and the expression of shock and stress proteins is greatly increased. Failure to fully cope with an oxidative stress can switch mitotic cells into a permanent growth-arrested, senescence-like state in which they may survive for long periods. Faced with even more severe oxidative stress, or the declining protective enzymes and adaptive capacity associated with aging, cells may "sacrifice themselves" by apoptosis, which protects surrounding healthy tissue from further damage. Only under the most severe oxidative stress conditions will cells undergo a necrotic death, which exposes surrounding tissues to the further vicissitudes of an inflammatory immune response. This remarkable array of systems for defense; damage removal, replacement, and repair; adaptation; growth modulation; and apoptosis make it possible for us to enjoy life in an oxygen-rich environment.

https://iubmb.onlinelibrary.wiley.com/doi/pdf/10.1080/713803728

Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems.

Differential regulation of antioxidant enzymes in response to oxidants.

Several studies suggest that active oxygen species (AOS) are involved in the development of asbestos-induced lung diseases. Experiments in this laboratory have focused on antioxidant enzym...

Antioxidant Defense Mechanisms in Asbestos-Induced Lung Disease

In this present study, a highly stable gum acacia -gold nanocomposite fabricated with food preservative agent natamycin (GA-AuNC-NT) was prepared via green science principles under in vitro conditions. Various characterisation techniques reveal highly stable structural, functional properties of the synthesised nanocomposite with marked antifungal activity and adsorption efficacy against congo red dye. The antifungal activity was investigated against the fungal strain Aspergillus ochraceopealiformis isolated from spoiled, expired bread. The well diffusion assay, fungal hyphae fragmentation assay and spore germination inhibition assay were used to determine the antifungal activity of the synthesised nanocomposite. Potential antifungal activity of the synthesised nanocomposite was confirmed by recording zone of inhibition, high rate of hyphae fragmentation and marked spore germination inhibition against the tested fungal strain. The molecular mechanism of antifungal activity was studied by measuring oxidative stress marker genes like catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) induction adopting quantitative real-time polymerase chain reaction (q RT-PCR). Among the various treatment, a notable reduction in all the tested marker genes expression was recorded in the nanocomposite treated fungal strain. Release profile studies using different solvents reveals sustained or controlled release of natamycin at the increasing periods. The synthesised nanocomposite's high safety or biocompatibility was evaluated with the Wistar animal model by determining notable changes in behavioural, biochemical, haematological and histopathological parameters. The synthesised nanocomposite did not exhibit any undesirable changes in all the tested parameters confirming the marked biosafety or biocompatibility. The nanocomposite was coated on the bread packaging material. The effect of packaging on the proximate composition, antioxidative enzymes status, and fungal growth of bread samples incubated under the incubation period were studied. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) studies reveal that the nanocomposite was effectively coated on the packaging material without changing size, shape, and functional groups. No changes in the proximate composition and antioxidative enzymes of the packaged bread samples incubated under different incubation periods reveal the nanocomposite's marked safety. The complete absence of the fungal growth also indicates the uniqueness of the nanocomposite. Further, the sorption studies revealed the utilisation of Langmuir mechanism and pseudo II order model successfully The present finding implies that the synthesised nanocomposite can be used as an effective, safe food preservative agent and adsorbent of toxic chemicals. 

Green chemistry principles for the synthesis of anti fungal active gum acacia-gold nanocomposite - natamycin (GA-AuNC-NT) against food spoilage fungal strain Aspergillus ochraceopealiformis and its marked Congo red dye adsprtion efficacy.

M. Manohar

Papers

Differential regulation of antioxidant enzymes in response to oxidants.

Antioxidant Defense Mechanisms in Asbestos-Induced Lung Disease

Green chemistry principles for the synthesis of anti fungal active gum acacia-gold nanocomposite - natamycin (GA-AuNC-NT) against food spoilage fungal strain Aspergillus ochraceopealiformis and its marked Congo red dye adsprtion efficacy.