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The occurrence of free fatty acids (FFAs) and the generation of reactive oxygen species (ROS) such as hydroxyl radicals (HO●) or hypochlorous acid (HOCl) is characteristic of inflammatory diseases, for instance, rheumatoid arthritis. Unsaturated fatty acids react with ROS yielding a variety of important products such as peroxides and chlorohydrins as primary and chain-shortened compounds (e.g., aldehydes and carboxylic acids) as secondary products. These modified fatty acids are either released from phospholipids by phospholipases or oxidatively modified subsequent to their release. There is increasing evidence that oligomeric products are also generated upon these processes. Fatty acid esters of hydroxy fatty acids (FAHFAs) are considered as very important products, but chlorinated compounds may be converted into dimeric and (with smaller yields) oligomeric products, as well. Our review is structured as follows: first, the different types of FFA oligomers known so far and the mechanisms of their putative generation are explained. Industrially relevant products as well as compounds generated from the frying of vegetable oils are also discussed. Second, the different opinions on whether dimeric fatty acids are considered as "friends" or "foes" are discussed. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the unique chemical compositions of plasma-activated water (PAW) and the potential antibacterial efficacy of PAW as a novel vaginal cleanser. We analyzed the ion compositions (four anions: F−, Cl−, NO3−, SO42−; five cations: Na+, NH4+, K+, Mg2+, Ca2+) of several formulations of PAW generated at different electrical powers (12 and 24 V) at various treatment time points (1, 10, and 20 min), and stay durations (immediate, 30, and 60 min). As treatment duration increased, hypochlorous acid (HOCl), Ca2+, and Mg2+ concentrations increased and Cl− concentration decreased. Higher electrical power and longer treatment duration resulted in increased HOCl levels, which acts to prevent the growth of general microorganisms. Notably, PAW had no antibacterial effects against the probiotic, Lactobacillus reuteri, which produces lactic acid and is important for vaginal health. These findings indicate that PAW contains HOCl and some cations (Ca2+ and Mg2+), which should help protect against pathogens of the vaginal mucosa and have a cleansing effect within the vaginal environment while not harming beneficial bacteria. [ABSTRACT FROM AUTHOR]

Abstract Background Droplets and aerosols produced during dental procedures are a risk factor for microbial and viral transmission. Unlike sodium hypochlorite, hypochlorous acid (HOCl) is nontoxic to tissues but still exhibits broad microbicidal effect. HOCl solution may be applicable as a supplement to water and/or mouthwash. This study aims to evaluate the effectiveness of HOCl solution on common human oral pathogens and a SARS-CoV-2 surrogate MHV A59 virus, considering the dental practice environment. Methods HOCl was generated by electrolysis of 3% hydrochloric acid. The effect of HOCl on human oral pathogens, Fusobacterium nucleatum, Prevotella intermedia, Streptococcus intermedius, Parvimonas micra, and MHV A59 virus was studied from four perspectives: concentration; volume; presence of saliva; and storage. HOCl solution in different conditions was utilized in bactericidal and virucidal assays, and the minimum inhibitory volume ratio that is required to completely inhibit the pathogens was determined. Results In the absence of saliva, the minimum inhibitory volume ratio of freshly prepared HOCl solution (45–60 ppm) was 4:1 for bacterial suspensions and 6:1 for viral suspensions. The presence of saliva increased the minimum inhibitory volume ratio to 8:1 and 7:1 for bacteria and viruses, respectively. Applying a higher concentration of HOCl solution (220 or 330 ppm) did not lead to a significant decrease in the minimum inhibitory volume ratio against S. intermedius and P. micra. The minimum inhibitory volume ratio increases in applications of HOCl solution via the dental unit water line. One week of storage of HOCl solution degraded HOCl and increased the minimum growth inhibition volume ratio. Conclusions HOCl solution (45–60 ppm) is still effective against oral pathogens and SAR-CoV-2 surrogate viruses even in the presence of saliva and after passing through the dental unit water line. This study indicates that the HOCl solution can be used as therapeutic water or mouthwash and may ultimately reduce the risk of airborne infection in dental practice.

Background: Droplets and aerosols produced during dental procedures are a risk factor for microbial and viral transmission. Unlike sodium hypochlorite, hypochlorous acid (HOCl) is nontoxic to tissues but still exhibits broad microbicidal effect. HOCl solution may be applicable as a supplement to water and/or mouthwash. This study aims to evaluate the effectiveness of HOCl solution on common human oral pathogens and a SARS-CoV-2 surrogate MHV A59 virus, considering the dental practice environment. Methods: HOCl was generated by electrolysis of 3% hydrochloric acid. The effect of HOCl on human oral pathogens, Fusobacterium nucleatum, Prevotella intermedia, Streptococcus intermedius, Parvimonas micra, and MHV A59 virus was studied from four perspectives: concentration; volume; presence of saliva; and storage. HOCl solution in different conditions was utilized in bactericidal and virucidal assays, and the minimum inhibitory volume ratio that is required to completely inhibit the pathogens was determined. Results: In the absence of saliva, the minimum inhibitory volume ratio of freshly prepared HOCl solution (45–60 ppm) was 4:1 for bacterial suspensions and 6:1 for viral suspensions. The presence of saliva increased the minimum inhibitory volume ratio to 8:1 and 7:1 for bacteria and viruses, respectively. Applying a higher concentration of HOCl solution (220 or 330 ppm) did not lead to a significant decrease in the minimum inhibitory volume ratio against S. intermedius and P. micra. The minimum inhibitory volume ratio increases in applications of HOCl solution via the dental unit water line. One week of storage of HOCl solution degraded HOCl and increased the minimum growth inhibition volume ratio. Conclusions: HOCl solution (45–60 ppm) is still effective against oral pathogens and SAR-CoV-2 surrogate viruses even in the presence of saliva and after passing through the dental unit water line. This study indicates that the HOCl solution can be used as therapeutic water or mouthwash and may ultimately reduce the risk of airborne infection in dental practice. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of eyelid hygiene using topical 0.01% hypochlorous acid (HOCL) through ultrasonic atomization after 2 weeks in patients with blepharitis. Design: Randomized controlled trial. Methods: Patients with blepharitis were randomized into two groups: topical 0.01% HOCL through ultrasonic atomization (HOCL group, 42 eyes) or eyelid scrubs (control group, 37 eyes). Patients in both groups received warm compresses twice daily and topical 0.5% levofloxacin three times a day. Primary outcomes were the ocular surface disease index scores (OSDI), lid margin redness, lid margin abnormalities, meibum expressibility, meibum quality, and noninvasive breakup time after 2 weeks. Secondary outcomes were conjunctiva redness, corneal fluorescein staining, and tear meniscus height. A questionnaire of treatment adherence with a free response section was administered to confirm patient compliance and comments. Results: Sixty-seven participants participated in this study. Both groups show an improvement in all primary outcomes, while statistically significant improvements in OSDI, lid margin redness, lid margin abnormality, meibum expressibility and quality are only limited to the HOCL group after 2 weeks of treatment (p < 0.05, p < 0.05, p < 0.001, p < 0.001 and p < 0.001, respectively). Subgroup analysis in HOCL reveals that only the change in lid margin abnormality and meibum expressibility in the mild–moderate meibomian glands loss patients at baseline has a statistically significant difference p < 0.05). Multiple linear regression shows that the improvement in OSDI is negatively associated with meibum expressibility score at the baseline (95% CI [−28.846, −1.815], p = 0.028). The patient compliance is 7.1 ± 2.0 in the HOCL group and 7.1 ± 1.8 in the control group (p > 0.05). No adverse events are reported. Conclusion: Topical 0.01% HOCL through ultrasonic atomization is a tolerable and effective eyelid hygiene treatment for blepharitis. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the unique chemical compositions of plasma-activated water (PAW) and the potential antibacterial efficacy of PAW as a novel vaginal cleanser. We analyzed the ion compositions (four anions: F−, Cl−, NO3−, SO42−; five cations: Na+, NH4+, K+, Mg2+, Ca2+) of several formulations of PAW generated at different electrical powers (12 and 24 V) at various treatment time points (1, 10, and 20 min), and stay durations (immediate, 30, and 60 min). As treatment duration increased, hypochlorous acid (HOCl), Ca2+, and Mg2+ concentrations increased and Cl− concentration decreased. Higher electrical power and longer treatment duration resulted in increased HOCl levels, which acts to prevent the growth of general microorganisms. Notably, PAW had no antibacterial effects against the probiotic, Lactobacillus reuteri, which produces lactic acid and is important for vaginal health. These findings indicate that PAW contains HOCl and some cations (Ca2+ and Mg2+), which should help protect against pathogens of the vaginal mucosa and have a cleansing effect within the vaginal environment while not harming beneficial bacteria.

Fibrosis is a chronic inflammation caused by the loss of innate compensational mechanisms. Naringin (NR) is a flavonoid with antineoplastic and anti-inflammatory effects. Here, we aimed to investigate the antifibrotic effects of NR and underlying mechanisms in a Hypochlorous acid (HOCl)-induced mouse model of skin fibrosis. A total of 24 six-week-old female BALB/c mice were randomly allocated into five groups: HOCl, Sham, PBS, HOCl + NR and DMSO and selected skin regions were treated for 6 weeks, until sacrifice. The histopathologic and collagenesis of skin resections were analyzed using H&E and PR staining. The mRNA levels of COL1, COL3 and αSMA genes were quantified. Serum samples were also used to evaluate TGF-β levels and LDH activity. HOCl could increase the relative collagen content, while NR administration on HOCl-treated biopsies decreased collagenesis. COL1, COL3 and αSMA mRNA levels were significantly increased among HOCl-treated skin samples, while NR treatment could decrease these mRNA levels of genes to the extent equal to the levels in the Sham group. Similarly, Naringin-treated samples could decrease TGF-β levels. We demonstrated that Naringin could exert protective effects against fibrotic complications of HOCL in skin tissue in vivo, by reducing the collagenesis and decreasing the levels of fibrosis-associated genes. [ABSTRACT FROM AUTHOR]

Alan G KabatPennsylvania College of Optometry, Salus University, Elkins Park, PA 19027, USAPurpose: Demodex folliculorum is a ubiquitous mite that can infest the eyelash follicles. Two commercial lid hygiene products have asserted their effectiveness in killing Demodex mites, yet there has never been a comparative trial between these two products. This study evaluated the demodicidal activity of 0.01% hypochlorous acid (HOCl) solution (Avenova; NovaBay Pharmaceuticals; Emeryville, CA) and 4% terpinen-4-ol (T4O) solution (Cliradex, Bio-Tissue; Miami, FL) in comparison to mineral oil (MO), a negative control.Methods: Live Demodex mites were obtained from volunteers. Samples were immersed in 1–2 drops of test solution: 0.01% HOCl, 4% T4O, or 100% MO. Samples were observed under the microscope every 10 mins for up to 90 mins. Kill time was defined as the elapsed time between the addition of test solution and all cessation of movement of the body, legs, mouth and pedipalps for a minimum of 60 seconds.Results: T4O demonstrated a mean kill time of 40±0.0 mins. HOCl had a mean kill time of 87.86±4.23 mins, with 79% of samples surviving the full 90 mins. In the MO group, all samples survived through the 90 min mark. Kill time was statistically significant in favor of T4O as compared to HOCl (p=0.0005). There was no statistically significant difference in kill time between HOCl and MO (p=0.25).Conclusion: 4% T4O effectively killed all adult mite samples within 40 mins of exposure. In contrast, the demodicidal activity of 0.01% HOCl was minimal, and comparatively similar to 100% MO.Keywords: Demodex, blepharitis, lid hygiene, tea tree oil, terpinen-4-ol, hypochlorous acid

While often regarded as a subset of metabolomics, lipidomics can better be considered as a field in its own right. While the total number of lipid species in biology may not exceed the number of metabolites, they can be modified chemically and biochemically leading to an enormous diversity of derivatives, many of which retain the lipophilic properties of lipids and thus expand the lipidome greatly. Oxidative modification by radical oxygen species, either enzymatically or chemically, is one of the major mechanisms involved, although attack by non-radical oxidants also occurs. The modified lipids typically contain more oxygens in the form of hydroxyl, epoxide, carbonyl and carboxylic acid groups, and nitration, nitrosylation, halogenation or sulfation can also occur. This article provides a succinct overview of the types of species formed, the reactive compounds involved and the specific molecular sites that they react with, and the biochemical or chemical mechanisms involved. In many cases, these modifications reduce the stability of the lipid, and breakdown products are formed, which themselves have interesting properties such as the ability to react with other biomolecules. Publications on the biological effects of modified lipids are growing rapidly, supporting the concept that some of these biomolecules have potential signaling and regulatory effects. The question therefore arises whether modified lipids represent an “epilipidome”, analogous to the epigenetic modifications that can control gene expression.

While often regarded as a subset of metabolomics, lipidomics can better be considered as a field in its own right. While the total number of lipid species in biology may not exceed the number of metabolites, they can be modified chemically and biochemically leading to an enormous diversity of derivatives, many of which retain the lipophilic properties of lipids and thus expand the lipidome greatly. Oxidative modification by radical oxygen species, either enzymatically or chemically, is one of the major mechanisms involved, although attack by non-radical oxidants also occurs. The modified lipids typically contain more oxygens in the form of hydroxyl, epoxide, carbonyl and carboxylic acid groups, and nitration, nitrosylation, halogenation or sulfation can also occur. This article provides a succinct overview of the types of species formed, the reactive compounds involved and the specific molecular sites that they react with, and the biochemical or chemical mechanisms involved. In many cases, these modifications reduce the stability of the lipid, and breakdown products are formed, which themselves have interesting properties such as the ability to react with other biomolecules. Publications on the biological effects of modified lipids are growing rapidly, supporting the concept that some of these biomolecules have potential signaling and regulatory effects. The question therefore arises whether modified lipids represent an "epilipidome", analogous to the epigenetic modifications that can control gene expression. [ABSTRACT FROM AUTHOR]

Honey is an easily accessible honey bee product, increasingly popular due to its biological activities and beneficial effects on human health. This study aimed to evaluate the capacity of samples of organic blossom honey and honeydew honey from southern Brazil exported to consumers worldwide to deactivate reactive oxygen (ROS) and nitrogen species (RNS), as well as to characterize their phenolic profile and the content of vitamin C. All the honey extracts analyzed displayed high content of phenolic compounds (49.79–117.68 mg gallic acid equivalents/g honey polyphenol extract) and high capacity to deactivate peroxyl radical (ROO•), hypochlorous acid (HOCl), and nitric oxide (NO•). Honeydew honeys exhibited up to 6 mg ascorbic acid per 100 g. Based on the phenolic profile as well as on ROS and RNS scavenging, all the organic honeys analyzed were grouped using multivariate analysis. Therefore, the analyzed eight organic honeys produced in southern Brazil can be considered as good sources of bioactive phenolic compounds. [ABSTRACT FROM AUTHOR]

• A novel water-soluble fluorescent probe with a large Stokes shift (about 115 nm) for detecting HOCl was designed. • The probe exhibited a remarkable fluorescence enhancement (˜ 227-fold). • The probe showed ultrasensitivity (DL = 3.30 nM) and fast response (<5 s) for HOCl. • The probe was successfully applied in tracking basal HOCl in living cells and zebrafish. Hypochlorous acid (HOCl) as a biologically important reactive oxygen species (ROS) plays crucial roles in the physiological and pathological processes. It is thus meaningful to explore an effective method for detecting basal HOCl in living systems. We herein report a large Stokes shift (about 115 nm) fluorescent probe LSS-HA for highly specific and ultrasensitive detection of HOCl with excellent water-solubility. Probe LSS-HA exhibited a remarkable fluorescence enhancement (˜ 227-fold) due to the adoption of high-quantum-yield fluorophore in aqueous solution. Besides, probe LSS-HA showed ultrasensitivity (detection limit is 3.30 nM) and fast response (<5 s) for HOCl. Furthermore, probe LSS-HA was successfully applied for imaging basal HOCl in living cells and zebrafish. [ABSTRACT FROM AUTHOR]

A near-infrared emitting fluorescent chemodosimeter for hypochlorous acid (HOCl), PAM, was designed and synthesized by modifying on the sulfonate porphyrin chromophore with a diaminomaleonitrile substituent to form Schiff-base as the chemodosimetric recognition unit. PAM behaved as a sensitive fluorescence "off-on" reactor to HOCl with satisfying anti-interference capacity over other latent disturbing analytes. The drastic fluorescence enhancement originated from the HOCl-promoted intramolecular cyclization to rigidify the molecular structure to a substituted imidazole, which effectively inhibited the C N isomerization. This chemical process is specific, expeditious and will not release extra compounds other than H 2 O. 1H NMR, FI-IR, HRMS, and spectral analysis confirmed the proposed mechanism. In addition to facilely synthesis, photo- and chemo-stable, PAM has outstanding features of fully water-soluble, low analytic limitation (6.3 nM), and positive linearity, which makes it practical to quantify HOCl in tap water and serum samples. Furthermore, PAM was efficiently leveraged for monitoring both exogenous and endogenous HOCl in living cells, as well as for differentiating between normal and cancer cells based on differences in basal HOCl levels. The versatility of this probe definitely provided a potential discovery tool for further elucidate the HOCl-associated neurological disorders. [Display omitted] • PAM demonstrates a HOCl-specific NIR emission based on a C N isomerization-intramolecular cyclization reaction. • The completely water-solubility and satisfactory recognition behavior enables PAM to be utilized in actual samples. • With CLSM, PAM can differentiate between normal and cancer cells based on differences in basal HOCl levels. [ABSTRACT FROM AUTHOR]

Monitoring native hypochlorous acid (HOCl) levels in living cells is of great significance because HOCl plays vital roles in various physiological and pathological processes. In this paper, we reported a novel biscoumarin-based two-photon fluorescent probe BCTP for monitoring native HOCl levels in living cells. Probe BCTP containing the recognition group of dimethylthiocarbamate moiety displayed preeminent selectivity towards HOCl over other various bioactive species (1 mM). Additionally, probe BCTP could quantitatively determine HOCl in the range of 0–3 nM with the detection limit of 27 pM. Moreover, probe BCTP could offer a promising tool for the real-time detection of HOCl (response time within 3 s). The potential applications of probe BCTP in the monitoring of native HOCl levels and the fluctuations of endogenous HOCl levels in living cells have been demonstrated by two-photon excitation microscopy with higher sensitivity. [ABSTRACT FROM AUTHOR]

Developing highly specific and ultrasensitive techniques for monitoring hypochlorous acid (HOCl) in the environment and living systems is very important to guarantee its safe use and disclose its diverse biological functions. We herein presented a simple water-soluble lysosome-targeted fluorescent probe TCRH for the detection of HOCl. Probe TCRH could sensitively monitor HOCl at the nanomolar levels with the detection limit of 0.12 nM. Additionally, probe TCRH with the response unit of thiocarbamate could selectively detect HOCl over other various analytes. Furthermore, probe TCRH showed an ultrafast response for HOCl (<3 s), implying that it could offer a real-time analytical assay of HOCl. Finally, probe TCRH was used for monitoring the basal lysosomal HOCl levels without exogenous stimuli and tracking the fluctuations of endogenous/exogenous HOCl levels in the lysosomes of live RAW 264.7 macrophage cells. [ABSTRACT FROM AUTHOR]

Highly specific and ultrasensitive fluorescent probes for tracking the intracellular native hypochlorous acid (HOCl) levels are urgently needed owing to its important molecular functions in the biological systems. In this contribution, a simple thiocarbamate-caged 7-hydroxycoumarin ( TCHC ) was developed as fluorescent probe for monitoring HOCl in live cells. Probe TCHC exhibited preeminent specificity towards HOCl over other various bioactive substances. Importantly, probe TCHC could sensitively detect HOCl in the range of 0–175 pM with the detection limit of 17 pM, which was attributed to the multiple fluorescence sensing mechanisms including photo-induced electron transfer (PET), intramolecular charge transfer (ICT), and the chlorination. Furthermore, probe TCHC displayed an instant response towards HOCl (<3 s), and thus the real-time detection of HOCl could be achieved. Finally, probe TCHC was successfully applied to monitor native HOCl and the fluctuations of endogenous HOCl levels in live cells. [ABSTRACT FROM AUTHOR]

Immunoglobulin light chain amyloidosis (AL) is a plasma cell disorder characterized by overproduction and deposition of monoclonal immunoglobulin (Ig) light chains (LC) or variable region fragments as amyloid fibrils in various organs and tissues. Much clinical evidence indicates that patients with AL amyloidosis sustain cardiomyocyte impairment and suffer from oxidative stress. We seek to understand the underlying biochemical pathways whose disruption or amplification during sporadic or sustained disease states leads to harmful physiological consequences and to determine the detailed structures of intermediates and products that serve as signposts for the biochemical changes and represent potential biomarkers. In this study, matrix-assisted laser desorption/ionization mass spectrometry provided extensive evidence for oxidative post-translational modifications (PTMs) of an amyloidogenic Ig LC protein from a patient with AL amyloidosis. Some of the tyrosine residues were heavily mono- or di-chlorinated. In addition, a novel oxidative conversion to a nitrile moiety was observed for many of the terminal aminomethyl groups on lysine side chains. In vitro experiments using model peptides, in-solution oxidation, and click chemistry demonstrated that hypochlorous acid produced by the myeloperoxidase – hydrogen peroxide – chloride system could be responsible for these and other, more commonly observed modifications. [ABSTRACT FROM AUTHOR]

[Display omitted] • 1O 2 can be generated in the anodic oxidation of H 2 O 2 in the presence of Cl−. • 1O 2 was directly confirmed by a near infrared imaging system. • 1O 2 plays an important role in E. coli inactivation in the presence of 1 mM H 2 O 2. • The formation of Cl-DBPs was mitigated considerably in the presence of H 2 O 2. • The implications for electrochemical water treatment were discussed. Due to its potential applications in decentralized water treatment systems, electrochemical synthesis of H 2 O 2 for water decontamination has been widely investigated in recent years. In this study, it is found that the anodic oxidation of the residual H 2 O 2 in the presence of Cl− can be an efficient electrochemical disinfection technology to guarantee the microbiological safety of the treated water. H 2 O 2 can be oxidized by HOCl generated at the anode to form singlet oxygen (1O 2). 1O 2 has been recognized as an important disinfectant in solar disinfection (SODIS) but it has not yet been reported in electrochemical disinfection. The generation of 1O 2 was directly confirmed by the detection of 1O 2 monomol emission using a near infrared imaging system. The concentration of 1O 2 can reach up to 1.64 pM in the anodic oxidation of H 2 O 2 with Cl−. 1O 2 plays an important role in Escherichia coli (E. coli) inactivation, and HOCl only plays a subordinate role in the presence of 1 mM H 2 O 2 due to its low concentration. For example, by adding up the inactivation of E. coli by sole H 2 O 2 and micro-concentration HOCl together only attribute to about 2 log in 60 min but 1O 2 itself can account for about 3 log. Besides, the formation of the chlorinated disinfection by-products (Cl-DBPs) was mitigated considerably benefited from the fast reduction of HOCl by H 2 O 2. These findings have potential implications for H 2 O 2 -based decentralized water treatment systems and provide a novel strategy for electrochemical disinfection because electrochlorination is having the same problems that chlorination has. [ABSTRACT FROM AUTHOR]

Abstract: Parkinson's disease is a progressive neurodegenerative disease in the elderly, and no cure or disease-modifying therapies exist. Several lines of evidence suggest that mitochondrial dysfunction and oxidative stress have a central role in the dopaminergic neurodegeneration of Parkinson's disease. In this context, mitochondria-targeted therapies that improve mitochondrial function may have great promise in the prevention and treatment of Parkinson's disease. In this review, we discuss the recent developments in mitochondria-targeted antioxidants and their potential beneficial effects as a therapy for ameliorating mitochondrial dysfunction in Parkinson's disease. This article is part of a Special Issue entitled: Misfolded Proteins, Mitochondrial Dysfunction, and Neurodegenerative Diseases. [Copyright &y& Elsevier]

Abstract: In the present work the scavenging capacity of coffee brews against ROS (ROO , H2O2, HO and HOCl) and RNS (NO and ONOO−) was evaluated and correlated with their bioactive compounds by multivariate analysis. It is the first time that the complete antioxidant capacity profile of coffee brews against different ROS and RNS is evaluated and that the capacity of coffee brews to scavenge NO is reported. The coffee brews were able to scavenge all the reactive species tested and possibly NO2 and CO3 −. The capacity of the coffee brews to scavenge ROO (2523 to 3673μmol TE/g), HO (IC50 =2.24 to 4.38μg/mL), NO (IC50 =3.07 to 5.67μg/mL) and ONOO− (IC50 =1.29 to 2.88μg/mL) was positively correlated to the contents of chlorogenic acids, chlorogenic acid lactones and p-coumaric acid, while the scavenging capacity against H2O2 (IC50 =336 to 531μg/mL) was positively correlated to the content of browned compounds, mainly melanoidins. The coffee brews showed to be potent HOCl scavengers (IC50 =5.12 to 11.20μg/mL), which was correlated to the contents of caffeic acid, 5-hydroxymethylfurfural and browned compounds. These results reinforce the hypothesis that the scavenging capacity against ROS/RNS is one of the mechanisms that can explain the association between the consumption of coffee brews and the decreased risk of chronic-degenerative diseases. [Copyright &y& Elsevier]

Highlights: [•] We exposed alveolar macrophages to cement dust samples from Nigeria and USA. [•] Increased membrane blebbing were observed in cells exposed to cement sample from USA. [•] Cement dust sample from USA induced increased oxidative stress and apoptosis. [•] Both cement samples induced increased IL-1β and TNF-α but decreased CINC-3 secretion. [•] The severity of cement dust toxicity may be factory dependent. [Copyright &y& Elsevier]

Abstract: Neutrophil recruitment and activation are principal events in inflammation. Upon activation neutrophils release myeloperoxidase (MPO), a heme enzyme, which binds to and transcytoses endothelial cells. Whereas the significance of the subendothelial deposition of MPO has evolved as a critical prerequisite for the enzyme's suppression of nitric oxide (NO⋅) bioavailability, the functional consequences of MPO binding to and interaction with endothelial and smooth muscle cells remain poorly understood. Cultured human endothelial cells (HUVECs) were exposed to MPO. Gene expression of the endothelin receptor type B (ETRB), which is critically involved not only in endothelin-1 clearance, but also in endothelin-mediated vasoconstriction, was significantly increased. Real time PCR, Western blotting and immunofluorescence confirmed up-regulation of ETRB in MPO-treated endothelial cells. Inhibition of MPO's enzymatic activity blunted the increase in ETRB protein expression. Treatment of the cells with the MAP kinase inhibitors PD98059 or SB203580 indicates that MPO activates ETRB expression via MAP kinase pathways. On human smooth muscle cells (HAoSMCs), which not only express the endothelin receptor type B (ETRB) but also express the endothelin receptor type A (ETRA), MPO also stimulated ETRB expression as opposed to ETRA expression, which remained unchanged. Functional ex vivo organ bath chamber studies with MPO-incubated rat femoral artery sections revealed increased ETRB agonist dependent constriction. Binding of MPO to endothelial and vascular smooth muscle cells increases expression of the endothelin receptor type B (ETRB) via classical MAP kinase pathways. This suggests that MPO not only affects vasomotion by reducing the bioavailability of vasodilating molecules but also by increasing responsiveness to vasoconstrictors, further advocating for MPO as a central, leukocyte-derived regulator of vascular tone. [Copyright &y& Elsevier]

Highlights: [•] With MPO inhibition, BT hardly increased apoptosis in HL-60 cells. [•] BT did not increase apoptosis in U937 cells, which express no MPO. [•] BT changed the expression levels of many genes in HL-60 cells. [•] BT mainly affected mRNA levels of genes related to apoptosis and antiapoptosis. [•] MPO inhibition dramatically suppressed the effects of BT on gene expression. [ABSTRACT FROM AUTHOR]

Abstract: Vitiligo is an acquired epidermal pigment loss of the skin. Oxidative stress is one of the major theories in the pathophysiology of vitiligo. FOXO3A is the forkhead members of the class O (FOXO) transcription factors, and plays an important role in cell cycle regulation, apoptosis, oxidative stress, and DNA repair. The aim of our study was to investigate FOXO3A gene polymorphisms and FOXO3A protein levels, activities of superoxide dismutase (SOD) and catalase antioxidant enzymes in vitiligo patients and healthy controls. Moreover, the level of plasma advanced oxidation protein products (AOPP) in subjects was evaluated to understand the possible role of protein oxidation in disease etiology. Study groups included 82 vitiligo patients and 81 unrelated healthy controls. FOXO3A polymorphisms were determined using polymerase chain reaction–restriction fragment length polymorphism method. FOXO3A levels and catalase activity were measured by ELISA whereas AOPP levels and SOD activity was measured by spectrophotometric analysis. We found a significant relationship between rs4946936 polymorphism of FOXO3A gene and vitiligo/active vitiligo patients (p=0.017; p=0.019 respectively), but not for rs2253310 (p>0.05). SOD activity and AOPP levels of vitiligo patient were increased compared with control group, whereas FOXO3A levels and catalase enzyme activity of vitiligo patient were decreased compared with control group (p<0.05). Our study indicates that rs4946936 of FOXO3A gene may associate susceptibility of vitiligo, especially active vitiligo. Moreover, our results confirm that oxidative stress may play a role in the pathophysiology of vitiligo. Further studies with larger samples are required to elucidate the role of FOXO3A in vitiligo. [Copyright &y& Elsevier]

Abstract: Background: The recent recognition that isoforms of the cellular NADPH-dependent oxidases, collectively known as the NOX protein family, participate in a wide range of physiologic and pathophysiologic processes in both the animal and plant kingdoms has stimulated interest in the identification, localization, and quantitation of their products in biological settings. Although several tools for measuring oxidants released extracellularly are available, the specificity and selectivity of the methods for reliable analysis of intracellular oxidants have not matched the enthusiasm for studying NOX proteins. Scope of review: Focusing exclusively on superoxide anion and hydrogen peroxide produced by NOX proteins, this review describes the ideal probe for analysis of O2 ― and H2O2 generated extracellularly and intracellularly by NOX proteins. An overview of the components, organization, and topology of NOX proteins provides a rationale for applying specific probes for use and a context in which to interpret results and thereby construct plausible models linking NOX-derived oxidants to biological responses. The merits and shortcomings of methods currently in use to assess NOX activity are highlighted, and those assays that provide quantitation of superoxide or H2O2 are contrasted with those intended to examine spatial and temporal aspects of NOX activity. Major conclusions: Although interest in measuring the extracellular and intracellular products of the NOX protein family is great, robust analytical probes are limited. [•] Several reliable methods for measurement of extracellular O2 ― and H2O2 by NOX proteins are available. [•] Chemiluminescent probes for both extracellular and intracellular O2 ― and H2O2 detection have shortcomings that limit their use. [•] Options for quantitation of intracellular O2 ― and H2O2 are very limited. [•] However, non-redox sensitive probes and genetically encoded reporters promise to provide spatial and temporal detection of O2 ― and H2O2. General significance: The widespread involvement of NOX proteins in many biological processes requires rigorous approaches to the detection, localization, and quantitation of the oxidants produced. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. [Copyright &y& Elsevier]

Abstract: Background: N-acetylcysteine (NAC) has been in clinical practice for several decades. It has been used as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication, doxorubicin cardiotoxicity, ischemia–reperfusion cardiac injury, acute respiratory distress syndrome, bronchitis, chemotherapy-induced toxicity, HIV/AIDS, heavy metal toxicity and psychiatric disorders. Scope of review: The mechanisms underlying the therapeutic and clinical applications of NAC are complex and still unclear. The present review is focused on the chemistry of NAC and its interactions and functions at the organ, tissue and cellular levels in an attempt to bridge the gap between its recognized biological activities and chemistry. Major conclusions: The antioxidative activity of NAC as of other thiols can be attributed to its fast reactions with OH, NO2, CO3 − and thiyl radicals as well as to restitution of impaired targets in vital cellular components. NAC reacts relatively slowly with superoxide, hydrogen-peroxide and peroxynitrite, which cast some doubt on the importance of these reactions under physiological conditions. The uniqueness of NAC is most probably due to efficient reduction of disulfide bonds in proteins thus altering their structures and disrupting their ligand bonding, competition with larger reducing molecules in sterically less accessible spaces, and serving as a precursor of cysteine for GSH synthesis. General significance: The outlined reactions only partially explain the diverse biological effects of NAC, and further studies are required for determining its ability to cross the cell membrane and the blood–brain barrier as well as elucidating its reactions with components of cell signaling pathways. [Copyright &y& Elsevier]

[Display omitted] • A novel benzocoumarin-based fluorescent probe BL for monitoring HOCl was designed and synthesized. • BL exhibits simple synthesis, excellent selectivity, fast response (<60 s), high sensitivity (DL, 5.64 nM). • BL was successfully applied to detect HClO spiked in tap water, 84 disinfectants and lake water, and has achieved satisfying recovery rates. • BL could readily fabricate solid-state visual sensors to be used to convenient detect HClO. • BL was nontoxic andsuccessfully used to monitor the variations of endogenous/exogenous HOCl in live RAW 264.7 macrophages. Hypochlorous acid (HOCl) is widely used in daily production and life. It is also a kind of endogenously produced reactive oxygen species (ROS) in the human immune system, plays a crucial role in many pathophysiological processes. This work designed and synthesized a novel based on benzocoumarin fluorescent probe BL for specific detection HOCl. BL has brilliant selectivity, high sensitivity (5.64 nM), fast response (60 s), moderate water-solubility. The intramolecular charge transfer (ICT) sensing mechanism of BL has been verified by fluorescence, UV, MS, and density functional theory (DFT) calculations. BL can make into a solid-state visual sensor to detect HOCl conveniently. BL was also applied to detect HClO spiked in tap water, 84 disinfectants, lake water, and satisfying recovery rates. Finally, BL was low toxic and used to track the variations of endogenous/exogenous HClO in living cells successfully. Totally, BL provides a powerful and reliable monitoring tool to reveal the biological functions of HOCl and ensure safe use. [ABSTRACT FROM AUTHOR]

Reaction of hypochlorous acid (HOCl) with imidazole (Im) taken as a model for the 5-membered ring of guanine, leading to the products 2-chloro- and 2-oxo-imidazoles was investigated at the B3LYP/6-31+G* and B3LYP/AUG-cc-pVDZ levels of density functional theory. For all cases, single point energy calculations were performed at the MP2/AUG-cc-pVDZ level of theory using the geometries optimised at the B3LYP/AUG-cc-pVDZ level. Intrinsic reaction coordinate calculations were performed to ensure genuineness of all the calculated transition states. Effect of aqueous media was investigated by solvating all the species involved in the reactions using the polarizable continuum model. It is found that 2-chloroimidazole (2-ClIm) can be formed following three different reaction schemes while 2-oxoimidazole (2-oxoIm) can be formed following two different reaction schemes. The calculated barrier energies show that formation of 2-oxoIm would be less favored than that of 2-ClIm, which explains the experimental observations on relative yields of 8-chlorodeoxyguanosine and 8-oxodeoxyguanosine. © 2007 Wiley Periodicals, Inc. J Comput Chem 2008 [ABSTRACT FROM AUTHOR]

Chronic periodontitis is a multi-factorial disease involving anaerobic bacteria and the generation of an inflammatory response, including the production of metalloproteinases, pro-inflammatory cytokines, and eicosanoids. Hypochlorous acid (HOCl) and taurine-Nmonochloramine (TauCl) are the end-products of the neutrophilic polymorphonuclear leukocyte (PMN) respiratory burst. They act synergistically to modulate the inflammatory response. In the extracellular environment, HOCl and TauCl may directly neutralize interleukin 6 (IL-6) and several metalloproteinases, while HOCl increases the capacity of α2-macroglobulin to bind Tumor Necrosis Factor-alpha, IL-2, and IL-6, and facilitates the release of various growth factors. TauCl inhibits the production of inflammatory mediators, prostaglandins, and nitric oxide. HOCl activates tyrosine kinase signaling cascades, generating an increase in the production of extracellular matrix components, growth factors, and inflammatory mediators. Thus, HOCl and TauCl appear to play a crucial role in the periodontal inflammatory process. Taken together, these findings may offer opportunities for the development of novel host-modulating therapies for the treatment of periodontitis. [ABSTRACT FROM AUTHOR]

Overproduction of reactive oxygen species or increased oxidative stress is considered a major mechanism involved in the pathogenesis of endothelial dysfunction, the initiation and progression of atherosclerosis and its adverse events. Evidence supports the importance of nitric oxide derived from endothelial nitric oxide synthase as a vasoprotective substance, and of vascular NAD(P)H oxidase-derived reactive oxygen species as important signaling molecules in vascular cells. Recent studies show that dysfunction of endothelial nitric oxide synthase in atherosclerosis generates O2− rather than nitric oxide, and that upregulation of vascular NAD(P)H oxidase is closely associated with atherosclerotic progression and plaque instability. [Copyright &y& Elsevier]

In an infection, polymorphonuclear neutrophils (PMN) become activated and they produce oxidizing compounds and elastase in the extracellular medium. Alpha-1-proteinase inhibitor (α1PI), a protease inhibitor which is inactivated by oxidants, is the main endogenous inhibitor of elastase helping to limit excessive elastase activity.This study evaluates the ability of a plant extract, Cola nitida nuts, to protect α1PI from inactivation by oxidizing compounds as reactive oxygen species.On the one hand, we have evaluated the direct effect of cola nut extract on neutrophil elastase, and on the H2O2 and myeloperoxidase (MPO)–H2O2 system via cell-free systems. Results showed that cola nut extract scavenges H2O2 and therefore protects α1PI from HOCl which is produced from the MPO–H2O2 system. Experiments also showed that cola extract has the capacity to limit elastase activity.On the other hand, we have worked on cellular systems including isolated PMN with the aim to study the effect of cola extract on PMN metabolism. PMN were stimulated with PMA, calcium ionophore or fMLP. Each stimulant possesses its own stimulation pathway. According to the inhibitory concentration obtained at 50%, the results on cellular systems led to the conclusion that cola extract can reduce elastase liberation from PMN.It can then be concluded that cola nut extract can protect α1PI from inactivation, and has an effect both on elastase liberation and elastase activity. The cola nut extract effect is rather biased towards a reduction in elastase release, thus limiting the injurious effects caused by this enzyme. [Copyright &y& Elsevier]

The neutrophil is a major effector cell of innate immunity. Exocytosis of granules and secretory vesicles plays a pivotal role in most neutrophil functions from early activation to the destruction of phagocytosed microorganisms. Neutrophil granules contain a multitude of antimicrobial and potentially cytotoxic substances that are delivered to the phagosome or to the exterior of the cell following degranulation. This review summarises current knowledge of granule biology and highlights the effects of neutrophil degranulation in the acute inflammatory response. [Copyright &y& Elsevier]

Menadione (MQ), a quinone used with cancer chemotherapeutic agents, causes cytotoxicity to endothelial cells (EC). Previous studies have suggested that MQ induces an oxidative stress and dysfunction in EC by either increasing hydrogen peroxide (H2O2) production or depleting intracellular glutathione (GSH), the main intracellular antioxidant. Since a primary function of EC is to form a barrier to fluid movement into tissues, protecting organs from edema formation and dysfunction, our aim was to see if MQ would cause a barrier dysfunction and to ascertain the mechanism. Using diffusional permeability to fluorescein isothiocyanate-labeled bovine serum albumin (FITC–BSA) as a measure of barrier function, we found that 15 μM MQ incubated with a bovine pulmonary artery EC (BPAEC) monolayer for 4 h produced a profound barrier failure (∼7-fold increase in permeability) with a parallel fall in glutathione, almost to depletion. These two events were highly correlated. Immunofluorescent imaging showed formation of paracellular holes consistent with a loss or rearrangement of cell–cell and cell–matrix adhesion molecules. H2O2 (100 μM), a concentration which gave about the same increase in permeability as MQ, only slightly decreased GSH concentration. Antioxidants, such as catalase (CAT) and dimethylthiourea (DMTU), which were able to block the H2O2-induced changes, had no effect on the MQ-induced permeability and GSH changes, suggesting that H2O2 was not involved in MQ-induced effects. MQ caused a severe EC cytotoxicity as judged by lactate dehydrogenase (LDH) leakage from the EC, whereas H2O2 caused only a minor increase. Also, MQ profoundly inhibited the activities of glucose-6-phosphate dehydrogenase (G6PDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), key thiol enzymes involved in glutathione and ATP metabolism, whereas H2O2 produced only a slight decrease in these activities. We conclude that the cytotoxicity of MQ and resulting barrier dysfunction correlate with GSH depletion and inactivation of key metabolic enzymes, compromising antioxidant defenses, rather than being consistent with H2O2-mediated oxidative stress. [Copyright &y& Elsevier]

The inflammatory bowel diseases (IBD; Crohn’s disease, ulcerative colitis) are a collection of chronic idiopathic inflammatory disorders of the intestine and/or colon. Although the pathophysiology of IBD is not known with certainty, a growing body of experimental and clinical data suggests that chronic gut inflammation may result from a dysregulated immune response to normal bacterial antigens. This uncontrolled immune system activation results in the sustained overproduction of reactive metabolites of oxygen and nitrogen. It is thought that some of the intestinal and/or colonic injury and dysfunction observed in IBD is due to elaboration of these reactive species. This review summarizes the current state-of-knowledge of the role of reactive oxygen species and nitric oxide in the pathophysiology of IBD. [Copyright &y& Elsevier]

• A simple dimethylthiocarbamate-based fluorescent probe for HOCl was synthesized. • The probe could selectively and sensitively detect nanomolar HOCl (DL = 0.9 nM). • The probe was successfully used to monitor native HOCl levels in living cells. • The probe could discriminate tumor cells and tissues from normal cells and tissues. The accurate and sensitive determination of basal hypochlorous acid (HOCl) in the biosystems is critical for unraveling its various physiological and pathological functions. Additionally, recent studies have shown that cancer cells possess higher concentration HOCl than normal cells. However, related studies about the discrimation of tumor cells and tissues from normal cells and tissues by using a simple HOCl probe have seldom been reported. Herein, we presented a simple, water-soluble, two-photon long-wavelength fluorescent probe TPFR for detecting HOCl with outstanding selectivity over other potential interfering substances. The fluorescence titration experiments demonstrated that probe TPFR was capable of quantitatively detecting 0–500 nM HOCl (DL = 0.9 nM). Additionally, the rapid response (<1 min) of probe TPFR for HOCl facilitated the detection of HOCl with high reactivity and short-time in the biosystems. The outstanding sensing performances of probe TPFR enabled it to be used to track intracellular basal HOCl and differentiate cancer cells from normal cells. Furthermore, probe TPFR was successfully used to discriminate tumor tissues from normal tissues in mice by two-photon excitation microscopy. [ABSTRACT FROM AUTHOR]

It is very important to detect native hypochlorous acid (HOCl) in the complex biosystems owing to the important roles of HOCl in the immune defense and the pathogenesis of numerous diseases. In this paper, a new p-aminophenylether-based fluorescent probe PAPE-HA was developed for specific detection of HOCl. Probe PAPE-HA could implement the quantitative detection of HOCl ranging from 0 to 1 μM and the detection limit was obtained as low as 1.37 nM. Additionally, probe PAPE-HA could reach a rapid response for HOCl (<2 min). Importantly, probe PAPE-HA with preeminent specificity and ultrasensitivity was proven to possess powerful capability of tracking native HOCl in live cells and zebrafish, and we thus anticipate that probe PAPE-HA could be used as a novel promising tool for revealing diverse cellular functions of HOCl., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study applies in situ production of hypochlorous acid (HOCl) to improve the therapeutic efficacy of platinum drugs. The phagocytic enzyme myeloperoxidase (MPO) is coated with two functional polyphenol derivatives (platinum prodrug polyphenols and PEG polyphenols) and ferric ion by metal phenolic coordination, which can shield MPO from degradation by other compounds in the blood. Moreover, the platinum prodrug can be reduced to cisplatin in cells and produce hydrogen peroxide (H 2 O 2 ). The MPO catalyzes the conversion of H 2 O 2 to HOCl in the intercellular environment. The as-prepared MPO Pt PEG nanoparticles (MPP NPs) can be employed as a reactive oxygen species cascade bioreaction to enhance platinum drug therapy. The MPP NPs show prolonged blood circulation and high tumor accumulation as evidenced by 89 Zr-based positron emission tomography imaging. The MPP NPs effectively inhibit tumor growth in vivo. As a first-in-class platform to harness the highly toxic HOCl in nanomedicine for cancer therapy, this strategy may open doors for further development of progressive therapeutic systems.

Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well characterized responses to other physiologically relevant oxidants, like peroxide or superoxide. Several RCS-sensitive transcription factors have been identified in bacteria, but most of them respond to multiple stressors whose damaging effects overlap with those of RCS, including reactive oxygen species and electrophiles. We have now used in vivo genetic and in vitro biochemical methods to identify and demonstrate that Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional activator of the AraC family, whose highly conserved cysteine residues are specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to strong, highly specific activation of expression of genes required for survival of RCS stress. These results demonstrate the existence of a widely conserved bacterial regulon devoted specifically to RCS resistance.