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We report on the physicochemical processes and the products of DNA damage involved in Ne-22 ion-beam radiation of hydrated (12 ± 3 H2O/nucleotide) salmon testes DNA at 77 K. Free radicals trapped at 77 K were identified using electron spin resonance (ESR) spectroscopy. The measurement of DNA damage using two different techniques of mass spectrometry revealed the formation of numerous DNA products. Results obtained by ESR spectroscopy showed that as the linear energy transfer (LET) of the ion-beam radiation increases along the beam track, the production of DNA radicals correspondingly increases until just before the Bragg peak is reached. Yields of DNA products along the ion-beam track were in excellent agreement with the radical production. This work is the first to use the combination of ESR spectroscopy and mass spectrometric techniques enabling a better understanding of mechanisms of radiation damage to DNA by heavy ion beams detailing the formation of DNA free radicals and their subsequent products.

Dropping during shipping and handling of liquid biopharmaceutical formulations has long been known to cause protein degradation and aggregation. On the other hand, accidental dropping of freeze-dried protein formulations is generally considered not a major issue for biopharmaceutical quality. Reports of stability and especially the underling degradation mechanism(s) during shipping and handling of freeze-dried protein formulations were rarely seen in literature. In this manuscript, we report an interesting phenomenon in which repeated dropping of freeze-dried monoclonal antibody X (mAb-X) formulation powder resulted in significant protein sub-visible particles (SbVPs) in the reconstituted liquid as determined by the sensitive particle analyzing technique micro-flow imaging (MFI). Free radicals were observed after repeated dropping by electron paramagnetic resonance (EPR). Formation of SbVPs could be partially inhibited by the free radical scavengers methionine and 3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidin-yloxy free radical (CTPO). The amount of free radicals and SbVPs was correlated to the sample temperature during dropping. Therefore we propose that the high temperature formed during dropping was probably the root cause for protein aggregation and free radical formation, which could further cause protein aggregation. Our observations suggest that similar to liquid protein formulations, dropping of freeze-dried protein formulations should also be avoided or mitigated.

Photobiomodulation is widely used in clinical practice, and there is increasing interest in using this tool to treat numerous dysfunctions in living organisms. Therefore, this study aimed to verify the action of blue and red light-emitting diode light in cells. Human fibroblast cell line (HFF-1) were irradiated by blue (470 nm) or red (658 nm) light at doses of 4 and 18 J/cm2, respectively. Laboratory analyses were carried out to check for viability, proliferation, cell death, and the formation of reactive oxygen and nitric oxide species. The blue light demonstrated cell protection potential by reducing free radical formation and protecting the cell membrane by decreasing double-stranded DNA strands. On the other hand, the red light showed less potential for cell protection due to the risk of associating more significant nitric oxide formation with increased reactive oxygen species formation, in addition to having a greater amount of extracellular DNA. Cell damage prevention is a potential beneficial effect of blue light at 18 J/cm2. Despite the consolidated effects of red light in treating wounds, there was a potential toxic effect of this wavelength in the doses studied. Given the above, new studies relating these parameters with pathological cells or aggressors that simulate damage may offer results that can better support clinical practice.

OBJECTIVES. The goal of the study was to determine whether reactive oxygen species (ROS) mediates cytomegalovirus (CMV)–induced labyrinthitis. STUDY DESIGN. Murine model of CMV infection. SETTING. University of Utah laboratory. SUBJECTS AND METHODS. Nrf2 knockout mice were inoculated with murine CMV. Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were then performed on these and uninfected controls. BALB/c mice were inoculated with murine CMV to determine whether a marker for ROS production, dihydroethidium (DHE), is expressed 7 days after inoculation. Finally, 2 antioxidants—D-methionine and ACE-Mg (vitamins A, C, and E with magnesium)—were administered 1 hour before and after infection in inoculated mice for 14 days. Temporal bones were harvested at postnatal day 10 for DHE detection. ABR and DPOAE testing was done at postnatal day 30. Scanning electron microscopy was also performed at postnatal day 30 to evaluate outer hair cell integrity. RESULTS. Nrf2-infected mice had worse hearing than uninfected mice (P < .001). A statistically significant increase in DHE fluorescence was detected in BALB/c-infected mice as compared with uninfected mice 7 days after inoculation. D-methionine- and ACE-Mg-treated mice demonstrated an attenuation of the DHE fluorescence and a significant improvement in ABR and DPOAE thresholds when compared with untreated infected controls (P

Photocatalytic degradation has been considered as an eco-friendly method for the removal of harmful antibiotics. Considering that the fundamental aspect of antibiotic photodegradation is a free radical reaction on the catalyst surface, boosting the generation of surface active free radicals is a direct and effective approach to promote the surface antibiotic oxidation reaction. However, rational regulation of the surface free radicals of photocatalysts is still a big challenge, and has also been rarely investigated. Herein, surface defect engineering was employed to introduce two different surface defect structures (i.e., two-coordinated nitrogen vacancies (N2C) on g-C3N4 and oxygen vacancies on TiO2) on the surface of a g-C3N4/TiO2 Z-scheme photocatalyst by one-step hydrogenation treatment, aiming to effectively modulate the surface active free radicals that directly dominate the surface redox reaction. The resulting defect-rich hydrogenated g-C3N4/TiO2 (H-CN/TiO2) Z-scheme heterojunction produced much more ˙OH and ˙O2− free radicals on the surfaces of TiO2 and g-C3N4, respectively, which would greatly facilitate the surface redox reactions in photocatalytic processes. As expected, the H-CN/TiO2 Z-scheme heterojunction exhibited obviously improved activity in photodegradation of tetracycline hydrochloride compared with those of defect-free photocatalysts. Meanwhile, the effect of defect structures on the surface free radicals of the H-CN/TiO2 photocatalyst was well explored and the photocatalytic mechanism was also discussed. This work paves the way for the regulation of free radical formation via surface defect engineering to further improve the photocatalytic activities of Z-scheme heterostructures.

Natural antioxidants have received tremendous attention over the last 3 decades. At the same time, the attitude to free radicals is slowly changing, and their signalling role in adaptation to stress has recently received a lot of attention. Among many different antioxidants in the body, taurine (Tau), a sulphur-containing non-proteinogenic β-amino acid, is shown to have a special place as an important natural modulator of the antioxidant defence networks. Indeed, Tau is synthesised in most mammals and birds, and the Tau requirement is met by both synthesis and food/feed supply. From the analysis of recent data, it could be concluded that the direct antioxidant effect of Tau due to scavenging free radicals is limited and could be expected only in a few mammalian/avian tissues (e.g., heart and eye) with comparatively high (>15–20 mM) Tau concentrations. The stabilising effects of Tau on mitochondria, a prime site of free radical formation, are characterised and deserve more attention. Tau deficiency has been shown to compromise the electron transport chain in mitochondria and significantly increase free radical production. It seems likely that by maintaining the optimal Tau status of mitochondria, it is possible to control free radical production. Tau’s antioxidant protective action is of great importance in various stress conditions in human life, and is related to commercial animal and poultry production. In various in vitro and in vivo toxicological models, Tau showed AO protective effects. The membrane-stabilizing effects, inhibiting effects on ROS-producing enzymes, as well as the indirect AO effects of Tau via redox balance maintenance associated with the modulation of various transcription factors (e.g., Nrf2 and NF-κB) and vitagenes could also contribute to its protective action in stress conditions, and thus deserve more attention.

An aerobic multicomponent reaction between monoalkyl-3,3-difluorocyclopropenes, pyridines, and arylthiols has been discovered to afford 3-arylsulfanyl-1-hydroxyindolizines. This reaction proceeds via intermediate C3-free indolizin-1-ols, easily forming free radicals in air. In the presence of arylthiols, potent radical traps, incorporation of arylsulfanyl substituent occurs at the C3 position of indolizin-1-ols by radical recombination. On the contrary, in an inert atmosphere, intermediate 1-hydroxyindolizines react with C- and N-electrophiles in a one-pot fashion. Novel, intensively colored 3-(tropon-2-yl)-indolizin-1-ols and high absorption coefficient 3-(tropolon-5-ylazo)-indolizin-1-ol dyes were synthesized in a multicomponent manner in 50-80% yields. The presence of an O-uncapped indolizin-1-ol moiety modulates the redox properties of the whole molecule, facilitating free radical formation, which is susceptible to further transformations. Three such examples were demonstrated: oxidative recyclization of 3-(2-hydroxyphenylsulfanyl)-indolizin-1-ol, auto-oxidation of substituted 3,3'-biindolizine-1,1'-diol, and diacetoxyiodobenzene (DAIB)-mediated dehydrogenation of 3-(tropolon-5-ylazo)-indolizin-1-ol. The latter reaction affords 3-((4,5-dioxocyclohepta-2,6-dien-1-ylidene)hydrazono)-3H-indolizin-4-ium-1-olate, a mesomeric betaine, strongly absorbing light on the borders of the visible range and showing a solvatochromic effect.

SUMMARY Loss of moisture in mature seeds of Quercus robur L. was associated with loss of viability, a rise in lipid peroxidation and build-up of free radicals. Radical-initiated damage was largely confined to the embryonic axes as their moisture contents declined to below 47 %. The accumulation of a stable free radical in axial tissue, detected by electron para-magnetic resonance (EPR), was indistinguishable from the EPR response previously shown in a moss on droughting and maize roots on desiccation. A minor higher-field component appeared to represent an intermediate stage in the sequence of free radical reactions associated with loss of water. Using seeds from freshly abscised fruits dried to different moisture contents, protective mechanisms against activated forms of oxygen were monitored in cotyledons and in embryonic axes. The two tissues exhibit distinctly different molecular defences against oxidative attack; that in the cotyledons being predominantly enzymatic, with relatively high and increasing activities of superoxide dismutase and glutathione reductase; that in the axes being largely through the anti-oxidants, ascorbic acid and alpha-tocopherol. We conclude that a decrease in enzymic protection against oxidative attack in the axes, associated with diminishing concentrations of alpha-tocopherol (and depletion of the precursor gamma-tocopherol) as moisture was lost, was directly linked with lipid peroxidation and free radical formation in the axes and that these events taken together may contribute to loss of viability in these recalcitrant seeds.

Numerous reactive oxygen species (ROS) entities exist, and hydrogen peroxide (H2O2) is very key among them as it is well known to possess a stable but poor reactivity capable of generating free radicals. Considered among reactive atoms, molecules, and compounds with electron-rich sites, free radicals emerging from metabolic reactions during cellular respirations can induce oxidative stress and cause cellular structure damage, resulting in diverse life-threatening diseases when produced in excess. Therefore, an antioxidant is needed to curb the overproduction of free radicals especially in biological systems (in vivo and in vitro). Despite the inherent properties limiting its bioactivities, polysaccharides from natural sources increasingly gain research attention given their position as a functional ingredient. Improving the functionality and bioactivity of polysaccharides have been established through degradation of their molecular integrity. In this critical synopsis; we articulate the effects of H2O2 on the degradation of polysaccharides from natural sources. Specifically, the synopsis focused on free radical formation/production, polysaccharide degradation processes with H2O2, the effects of polysaccharide degradation on the structural characteristics; physicochemical properties; and bioactivities; in addition to the antioxidant capability. The degradation mechanisms involving polysaccharide’s antioxidative property; with some examples and their respective sources are briefly summarised.

The effects of low and high frequency ultrasound on the production of volatile compounds along with their derivation and corresponding off-flavours in milk and milk products are discussed in this review. The review will simultaneously discuss possible mechanisms of applied ultrasound and their respective chemical and physical effects on milk components in relation to the production of volatile compounds. Ultrasound offers potential benefits in dairy applications over conventional heat treatment processes. Physical effects enhance the positive alteration of the physicochemical properties of milk proteins and fat. However, chemical effects propagated by free radical generation cause redox oxidations which in turn produce undesirable volatile compounds such as aldehydes, ketones, acids, esters, alcohols and sulphur, producing off-flavours. The extent of volatile compounds produced depends on ultrasonic processing conditions such as sonication time, temperature and frequency. Low frequency ultrasound limits free radical formation and results in few volatile compounds, while high ultrasonic frequency induces greater level of free radical formation. Furthermore, the compositional variations in terms of milk proteins and fat within the milk systems influence the production of volatile compounds. These factors could be controlled and optimized to reduce the production of undesirable volatiles, eliminate off-flavours, and promote the application of ultrasound technology in the dairy field.

Background X-rays are defined as ionizing radiation and hydrolyze the water, causing free radical formation. Oxidative stress is the damage that occurs in cells due to the lack of antioxidants, which detoxifies them, with the increased production of free radicals that occur during normal cellular metabolism. Purpose To examine the acute effects of computed tomography (CT), i.e. ionizing radiation, on oxidative stress and antioxidant defense mechanisms. Material and Methods The study included a total of 53 patients that were selected among the patients that underwent non-contrast full-body CT. Malondialdehyde (MDA) and reduced glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities were investigated in blood samples taken from patients. Results The post-scan levels of MDA increased significantly while the post-scan levels of GSH, SOD, and CAT decreased significantly compared to their pre-scan levels. Conclusion CT, which is a widely used X-ray imaging technique and has numerous known side effects, was found to increase the levels of MDA, which is an indicator of oxidative stress, and to decrease the levels of some antioxidants including GSH, SOD, and CAT.

The residue lysine 28 (K28) is known to form an important salt bridge that stabilizes the Aβ amyloid structure, and acetylation of lysine 28 (K28Ac) slows the Aβ42 fibrillization rate but does not affect fibril morphology. On the other hand, acetylation of lysine 16 (K16Ac) residue greatly diminishes the fibrillization property of Aβ42 peptide and also affects its toxicity. This is due to the fact that lysine 16 acetylated amyloid beta peptide forms amorphous aggregates instead of amyloid fibrils. This is likely a result of increased hydrophobicity of the K16-A21 region due to K16 acetylation, as confirmed by molecular dynamic simulation studies. The calculated results show that the hydrophobic patches of aggregates from acetylated peptides were different when compared to wild-type (WT) peptide. K16Ac and double acetylated (KKAc) peptide aggregates show significantly higher cytotoxicity compared to the WT or K28Ac peptide aggregates alone. However, the heterogeneous mixture of WT and acetylated Aβ42 peptide aggregates exhibited higher free radical formation as well as cytotoxicity, suggesting dynamic interactions between different species could be a critical contributor to Aβ pathology.

The &beta, amyloid (A&beta, ) peptide plays a key role in the pathogenesis of Alzheimer&rsquo, s disease. The methionine (Met) residue at position 35 in A&beta, C-terminal domain is critical for neurotoxicity, aggregation, and free radical formation initiated by the peptide. The role of Met in modulating toxicological properties of A&beta, most likely involves an oxidative event at the sulfur atom. We therefore investigated the one- or two-electron oxidation of the Met residue of A&beta, 25-35 fragment and the effect of such oxidation on the behavior of the peptide. Bicarbonate promotes two-electron oxidations mediated by hydrogen peroxide after generation of peroxymonocarbonate (HCO4&minus, PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO3&bull, &minus, ). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of A&beta, to aggregate. Conversely, CO3&bull, causes the one-electron oxidation of methionine residue to sulfur radical cation (MetS&bull, +). The formation of this transient reactive intermediate during A&beta, oxidation may play an important role in the process underlying amyloid neurotoxicity and free radical generation.

The control of bleaching reaction is important in hair bleaching and laundry detergents to ensure quality of the final product. A better understanding of the reaction mechanisms is needed to minimize product failures. 31P NMR-spectroscopy-based spin trap technique was employed to detect and quantify the free radical species that were generated in different bleaching solutions. These solutions contained the key actives in an alkaline hair colorant/bleaching product, an ammonium salt and hydrogen peroxide at pH = 10. Generally, the main radical species detected in hair oxidative coloring or bleaching processes, were hydroperoxyl/superoxide radicals HO2·/O2.-, amino radicals ·NH2 and hydroxyl radicals ·OH. Their amounts showed a variation based on the chemical composition of the bleaching systems and the metal ion content. The generation of free radicals from reactions between transition metal ions, such as copper, and hydrogen peroxide at pH = 10 was evaluated. In the absence of chelating agents, the copper ions generated a significant level of hydroxyl radicals in a Fenton-like reaction with hydrogen peroxide at pH = 10. Besides that, an increase in copper ion content led to an increase of amino radical ·NH2, whereas the concentration of superoxide radical O2·- decreased which was not yet well reported in the previous literature. The effect of chelating agents like ethylenediaminetetraacetic acid (EDTA), tetrasodium-iminodisuccinate (IDS), a mixture of basic amino acids and dicarboxylic acid on free radical formation was investigated in the presence of binary Cu2+-Ca2+ bleaching systems. As expected, in the binary Cu2+-Ca2+ ion system EDTA did not suppress hydroxyl radical formation effectively, but the mixture containing sodium succinate, lysine and arginine reduced hydroxyl radical formation, whereas IDS (nearly) completely inhibited hydroxyl radical formation. The results indicated that each bleaching solution has its characteristic performance and damage profile. Whereas the reactivity can be controlled by the usage of chelating agents.

This study examined to what extent the human cerebral and femoral circulation contribute to free radical formation during basal and exercise-induced responses to hypoxia. Healthy participants (5♂, 5♀) were randomly assigned single-blinded to normoxic (21% O2) and hypoxic (10% O2) trials with measurements taken at rest and 30 min after cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled from the brachial artery (a), internal jugular and femoral veins (v) for non-enzymatic antioxidants (HPLC), ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), lipid hydroperoxides (LOOH) and low density lipoprotein (LDL) oxidation (spectrophotometry). Cerebral and femoral venous blood flow was evaluated by transcranial Doppler ultrasound (CBF) and constant infusion thermodilution (FBF). With 3 participants lost to follow up (final n = 4♂, 3♀), hypoxia increased CBF and FBF (P = 0.041 vs. normoxia) with further elevations in FBF during exercise (P = 0.002 vs. rest). Cerebral and femoral ascorbate and α-tocopherol consumption (v a) and increased LDL oxidation during hypoxia (P < 0.043-0.049 vs. normoxia) implying free radical-mediated lipid peroxidation subsequent to inadequate antioxidant defense. This was pronounced during exercise across the femoral circulation in proportion to the increase in local O2 uptake (r = -0.397 to -0.459, P = 0.037-0.045) but unrelated to any reduction in PO2. These findings highlight considerable regional heterogeneity in the oxidative stress response to hypoxia that may be more attributable to local differences in O2 flux than to O2 tension.

Honey is known for its wound healing potential. In this study we investigated free radical formation and inhibition in different honeys and the influence on bacterial growth inhibition. alpha-Oxaldehydes and free amino acids were shown to be present in manuka and non-manuka honeys. With electron spin resonance we measured that methylglyoxal (MG) and glyoxal (GO) form different carbon centered radicals under the influence of either hydrogen peroxide or arginine and lysine. These radicals were also formed in a combination of alpha-oxaldehydes and amino acids in artificial honey, which was quantified by the cytochrome C assay. Also, a strong bactericidal activity for MG and GO (minimum concentration 0.6 and 1.25 mM) was shown against different bacterial strains. Interestingly, honeys with a high MG content were shown to be better free radical scavengers for hydroxyl and superoxide radicals, implying a complex mechanism for free radical donation and scavenging in honey.

Grape seeds are a relatively abundant source of oil and bioactive compounds. To use this byproduct, the current work aimed to optimize the ultrasound-assisted extraction (UAE) of grape-seed oil to obtain greater process yield and minimize free radical formation in the oil.; Results: The optimal condition was 15 °C with an ultrasonic wave amplitude of 42 µm, leading to a process yield of 82.9% and content of free radicals of 14.7 × 1017 kg-1 and 3.4 × 1018 kg-1 for samples stored for 7 and 30 days, respectively. No significant differences in fatty acid composition and acidity and iodine values were observed between samples. The oil obtained by ultrasound had greater phenolic compound content and antioxidant activity by ferric reduction than the control sample (without ultrasound application). However, higher content of free radicals and peroxide value was observed.; Conclusion: Sonication improved extraction yield when compared to the process without ultrasound application. Moreover, UAE favored the extraction of phenolic compounds. As it enhanced process yield with the minimum formation of free radicals, UAE is a promising oil-extraction technology. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

Increasing studies focus on the degradation of polysaccharides by free radicals. The review mainly provides an overview of degradation of polysaccharides by free radicals generated from hydrogen peroxide (H2O2). Evidence suggests that free radicals generated from H2O2 can be generated by various mechanisms. It broke glycosidic bonds mainly through hydrogen abstraction, causing the degradation of polysaccharides. Its degradation efficiency is affected by many factors, such as the concentration of polysaccharides and H2O2, temperature and pH. In addition, free radical degradation could change the physicochemical and structural properties of polysaccharides, such as water solubility, thermal stability, molecular weight, monosaccharide composition, apparent morphology, and chain conformation, but it had little effects on the primary structure of polysaccharides. Besides, free radical degradation could also improve the bioactivities of polysaccharides, including antioxidant, antitumor and anticoagulant activities.

BACKGROUND The pathology of diabetes is associated with several mechanisms, one of which is oxidative stress (OS). The relationship between OS and diabetic complications has been extensively investigated. OS has been suggested to be involved in the genesis of both macroand microangiopathy. In contrast, the relationship between OS and insulin action is a neglected research area. OBJECTIVES The aim of this study is to elucidate the effect of glycemic control in type 2 diabetic patients by following the serum levels of some real-time oxidative stress biomarkers. MATERIAL AND METHODS The study group consisted of 53 type 2 diabetic patients (31 with poor glycemic control and 22 with good glycemic control) and 24 healthy control subjects. The oxidative stress biomarkers (ROS, Asc• and •NO) were measured by using electron paramagnetic resonance spectroscopy (EPR) methods and compared with clinical parameters. RESULTS The statistically significantly higher levels of ROS products and •NO in type 2 diabetic patients in both groups compared to controls mean that the oxidation processes take place at the time the survey is performed. Free radical overproduction persists after the normalization of the glucose levels, and oxidative stress may be involved in the "metabolic memory" effect. This is confirmed by the positive correlation between ROS levels/•NO and average blood glucose levels, triglycerides, and total cholesterol. Furthermore, the low level of the ascorbate radical in both diabetes groups compared to controls confirmed an increase in oxidation processes. CONCLUSIONS Higher levels of real-time biomarkers show that intensive insulin treatment does not lead to the expected decrease in oxidative processes involving ROS and •NO, probably due to "metabolic memory".

The processes of electrical charge accumulation and dissipation in dielectric materials are critical to spacecraft construction and operational anomaly resolution. Electrical conductivity, and therefore surface potential, of radiation-damaged materials undergoes unpredicted changes while on orbit. The space environment causes fundamental modifications in the chemical structure of spacecraft materials by breaking intermolecular bonds and creating free radicals that act as space charge traps. Over time, free radicals react with each other and the material recovers. The rates of free radical formation and loss determine the dynamics of the conductivity of spacecraft materials. Lack of knowledge about dynamic aging is a major impediment to accurate modeling of spacecraft behavior over its mission life. This paper presents an investigation of the chemical and physical properties of polyimide (PI) films during and after irradiation with high-energy (90 keV) electrons. The constant voltage method was utilized to monitor material conductivity during the recovery process. To quantify the concentration of free radicals within the irradiated material, the electron paramagnetic resonance technique was used. Changes in the infrared (IR) absorption profile of irradiated materials during the recovery process were identified using the directional-hemispherical reflectance technique coupled with the Fourier transform IR spectroscopy. This physical/chemical collaboration allowed correlation of chemical changes in PI with the dynamic nature of spacecraft material aging.