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Changes to the redox status of biological systems have been implicated in the pathogenesis of a wide variety of disorders including cancer, Ischemia-reperfusion (I/R) injury and neurodegeneration. In times of metabolic stress e.g. ischaemia/reperfusion, reactive oxygen species (ROS) production overwhelms the intrinsic antioxidant capacity of the cell, damaging vital cellular components. The ability to quantify ROS changes in vivo, is therefore essential to understanding their biological role. Here we evaluate the suitability of a novel reversible profluorescent probe containing a redox-sensitive nitroxide moiety (methyl ester tetraethylrhodamine nitroxide, ME-TRN), as an in vivo, real-time reporter of retinal oxidative status. The reversible nature of the probe's response offers the unique advantage of being able to monitor redox changes in both oxidizing and reducing directions in real time. After intravitreal administration of the ME-TRN probe, we induced ROS production in rat retina using an established model of complete, acute retinal ischaemia followed by reperfusion. After restoration of blood flow, retinas were imaged using a Micron III rodent fundus fluorescence imaging system, to quantify the redox-response of the probe. Fluorescent intensity declined during the first 60 min of reperfusion. The ROS-induced change in probe fluorescence was ameliorated with the retinal antioxidant, lutein. Fluorescence intensity in non-Ischemia eyes did not change significantly. This new probe and imaging technology provide a reversible and real-time response to oxidative changes and may allow the in vivo testing of antioxidant therapies of potential benefit to a range of diseases linked to oxidative stress., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The radical reactions of dimethylsulfoxide (DMSO) and tetrahydrothiophene-1-oxide (THTO) with reactive oxygen species (ROS) in the presence of a nitroxide radical scavenger have been evaluated both synthetically and in analytical practice. Fenton-mediated generation of oxygen-centred radicals produced several unusual products that reflect the fragmentation and ring-opening radical mechanisms of DMSO and THTO respectively. Addition of pollution-derived ROS to DMSO/THTO nitroxide solutions produced LC-MS detectable amounts of the same products isolated from the larger-scaled Fenton reactions. For air pollution analysis, these results highlight the complexity surrounding DMSO reactivity and fragmentation, and indicate that THTO produces simpler outcomes that should facilitate analysis of the processes involved. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) present on or generated by particulate matter (PM) have been implicated in PM-induced health effects. Methodologies to quantify ROS concentrations vary widely, both in detection and collection methods. However, there is currently an increasing emphasis on rapid collection and measurement due to observations of short half-life ROS. To address this problem, this paper details the design and characterization of a novel instrument for the measurement of PM-bound ROS named the Particle Into Nitroxide Quencher (PINQ). This instrument combines the 9,10-bis (phenylethynyl) anthracene-nitroxide (BPEAnit) ROS assay in conjunction with a purpose-built aerosol collection device, the insoluble aerosol collector (IAC). The IAC continuously collects PM regardless of size or chemistry directly into a liquid sample with a collection efficiency of > 0.97 and a cut-off size of < 20 nm. The sampling time resolution of the PINQ is 1 min, with a limit of detection (LOD) of 0.08 nmol m -3 in equivalent BPEAnit-Me concentration per volume of air. This high sample time resolution and sensitivity is achieved due to a combination of the highly concentrated IAC liquid sample, minimized liquid sample volume, and the rapid reaction and stability of the BPEAnit probe. [ABSTRACT FROM AUTHOR]

This manuscript details the application of a profluorescent nitroxide (PFN) for the online quantification of radical concentrations on particulate matter (PM) using an improved Particle Into Nitroxide Quencher (PINQ). A miniature flow-through fluorimeter developed specifically for use with the 9,10-bis(phenylethynyl)anthracene-nitroxide (BPEAnit) probe was integrated into the PINQ, along with automated gas phase corrections through periodic high efficiency particle arrestor (HEPA) filtering. The resulting instrument is capable of unattended sampling and was operated with a minimum time resolution of 2.5 min. Details of the fluorimeter design and examples of data processing are provided, and results from a chamber study of side-stream cigarette smoke and ambient monitoring campaign in Guangzhou, China are presented. Primary cigarette smoke was shown to have both short-lived (t1/2 = 27 min) and long-lived (t1/2 = indefinite) PM-bound reactive oxygen species (ROS) components which had previously only been observed in secondary organic aerosol (SOA). [ABSTRACT FROM AUTHOR]

Dual-acting hybrid anti-oxidant/anti-inflammatory agents were developed employing the principle of pharmacophore hybridization. Hybrid agents were synthesized by combining stable anti-oxidant nitroxides with conventional non-steroidal anti-inflammatory drugs (NSAIDs). Several of the hybrid nitroxide-NSAID conjugates displayed promising anti-oxidant and anti-inflammatory effects on two Non-Small Cell Lung Cancer (NSCLC) cells (A549 and NCI-H1299) and in ameliorating oxidative stress induced in 661 W retinal cells. One ester-linked nitroxide-aspirin analogue ( 27 ) delivered better anti-inflammatory effects (cyclooxygenase inhibition) than the parent compound (aspirin), and also showed similar reactive oxygen scavenging activity to the anti-oxidant, Tempol. In addition, a nitroxide linked to the anti-inflammatory drug indomethacin ( 39 ) significantly ameliorated the effects of oxidative stress on 661 W retinal neurons at efficacies greater or equal to the anti-oxidant Lutein. Other examples of the hybrid conjugates displayed promising anti-cancer activity, as demonstrated by their inhibitory effects on the proliferation of A549 NSCLC cells. [ABSTRACT FROM AUTHOR]

Particle emissions, volatility, and the concentration of reactive oxygen species (ROS) were investigated for a pre-Euro I compression ignition engine to study the potential health impacts of employing ethanol fumigation technology. Engine testing was performed in two separate experimental campaigns with most testing performed at intermediate speed with four different load settings and various ethanol substitutions. A scanning mobility particle sizer (SMPS) was used to determine particle size distributions, a volatilization tandem differential mobility analyzer (V-TDMA) was used to explore particle volatility, and a new profluorescent nitroxide probe, BPEAnit, was used to investigate the potential toxicity of particles. The greatest particulate mass reduction was achieved with ethanol fumigation at full load, which contributed to the formation of a nucleation mode. Ethanol fumigation increased the volatility of particles by coating the particles with organic material or by making extra organic material available as an external mixture. In addition, the particle-related ROS concentrations increased with ethanol fumigation and were associated with the formation of a nucleation mode. The smaller particles, the increased volatility, and the increase in potential particle toxicity with ethanol fumigation may provide a substantial barrier for the uptake of fumigation technology using ethanol as a supplementary fuel. [ABSTRACT FROM AUTHOR]

The chemical composition and evolution of secondary organic aerosol (SOA) in theatmosphere represents one of the largest uncertainties in our current understanding of airquality. Studies suggest that reactive oxygen species (ROS), either present in ambient aerosoland exogenously delivered or generated by particle components in vivo, are potentially amajor contributor to aerosol toxicity. Several methods are currently available for probingROS concentrations in aerosol, however, the role of radicals and reactive intermediatesin both the formation and ageing of aerosol, as well as their contribution to thehealth-relevant properties of ambient aerosol, at present remains highly uncertain.Recently, a study by Stevanovic et al.1 introduced the profluorescent spin trap BPEAnit(9,10-bis-(phenylethynyl)-anthracene-nitroxide), where they subsequently used this methodto quantify particle-bound radicals in aerosol generated from the combustion of biomaterialand fuel. In this work, BPEAnit is applied to study the concentrations of particle-boundradicals in SOA. Radical concentrations were estimated for SOA generated from theozonolysis of α-pinene, β-caryophyllene and limonene in a flow tube, to probethe assays response to SOA formed from biogenic volatile organic compounds.SOA is captured in an impinger containing BPEAnit/DMSO, before subsequentanalysis using fluorescent spectroscopy. Using this method, a pseudo-1st orderrate constant of k = 7.3 ± 1.7 × 10−3 s−1 was derived for the overall decay oforganic radicals in α-pinene SOA, implying a radical lifetime on the order of severalminutes. Furthermore, building on our recent work in Giorio et al.,2 the spin trap PBN(N-tert-butyl-α-phenylnitrone) was used to trap Criegee intermediates (CIs) present in theaerosol phase, with the resulting adducts analysed using high performance liquidchromatography high-resolution mass spectrometry. Experiments were conducted with thismethod using SOA generated from β-caryophyllene ozonolysis in a flow tube,demonstrating the technique&#x2019;s unique capability to detect multiple CIs present in SOAand representing the first detection of CIs in organic aerosol. Detected CIs wereestimated to constitute approximately 0.8% of the total particle mass, demonstratingthe potential of this method to provide quantitative data of condensed phase CIs. [ABSTRACT FROM AUTHOR]