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ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEvaluation of the antioxidant and prooxidant actions of gallic acid and its derivativesOkezie I. Aruoma, Antonia. Murcia, John. Butler, and Barry. HalliwellCite this: J. Agric. Food Chem. 1993, 41, 11, 1880–1885Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/jf00035a014https://doi.org/10.1021/jf00035a014research-articleACS PublicationsRequest reuse permissionsArticle Views2733Altmetric-Citations320LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Abstract All clinically-approved and many novel gadolinium (Gd)-based contrast agents used to enhance signal intensity in magnetic resonance imaging (MRI) are optically silent. To verify MRI results, a “gold standard” that can map and quantify Gd down to the parts per million (ppm) levels is required. Nuclear microscopy is a relatively new technique that has this capability and is composed of a combination of three ion beam techniques: scanning transmission ion microscopy, Rutherford backscattering spectrometry, and particle induced X-ray emission used in conjunction with a high energy proton microprobe. In this proof-of-concept study, we show that in diseased aortic vessel walls obtained at 2 and 4 h after intravenous injection of the myeloperoxidase-senstitive MRI agent, bis-5-hydroxytryptamide-diethylenetriamine-pentaacetate gadolinium, there was a time-dependant Gd clearance (2 h = 18.86 ppm, 4 h = 8.65 ppm). As expected, the control animal, injected with the clinically-approved conventional agent diethylenetriamine-pentaacetate gadolinium and sacrificed 1 week after injection, revealed no significant residual Gd in the tissue. Similar to known in vivo Gd pharmacokinetics, we found that Gd concentration dropped by a factor of 2 in vessel wall tissue in 1.64 h. Further high-resolution studies revealed that Gd was relatively uniformly distributed, consistent with random agent diffusion. We conclude that nuclear microscopy is potentially very useful for validation studies involving Gd-based magnetic resonance contrast agents.

Peroxynitrite (ONOO − ) is a cytotoxic species, formed by the reaction between nitric oxide and superoxide free radicals, that may be involved in inflammation. In this study we have investigated the effect of peroxynitrite on plasma extravasation and microvascular blood flow in the dorsal skin and on nociceptive responses in the hind paw of the rat. Male Wistar rats were anaesthetized and their dorsal skin shaved. Plasma extravasation was measured by the extravascular accumulation of 125 I‐labelled albumin over 0–45 min and 0–240 min. Blood flow was measured by laser‐Doppler flowmetry over 0–240 min. Studies in the hind paw were carried out in the conscious rat. Hind paw weight changes were determined by volume displacement and nociception by a mechanical hyperalgesia technique. Intradermal (i.d.) peroxynitrite (100–200 nmol site −1 ) produced a significant ( P <0.01) dose‐dependent increase in plasma extravasation in dorsal skin over 0–45 min which was not increased over 45–240 min. Plasma extravasation was significantly ( P <0.001) decreased in rats pretreated with the anti‐inflammatory steroid dexamethasone (1 mg kg −1 , i.v.; −180 min), but not modulated by treatment with the hydrogen peroxide deactivator catalase (2200 u site −1 ), or the superoxide scavenger superoxide dismutase (500 u site −1 ), effective doses of the tachykinin NK 1 antagonist SR140333 (1 nmol site −1 ), the cyclo‐oxygenase inhibitor indomethacin (358 μmol site −1 ), or combined pretreatment with mepyramine (histamine H 1 ‐receptor antagonist; 2.8 nmol site −1 ) and methysergide (5‐HT antagonist; 1.9 nmol site −1 ). Microvascular blood flow was significantly ( P <0.05) increased 30 and 120 min after i.d. peroxynitrite (100 nmol site −1 ) in dorsal skin and remained raised until the end of the recording period (240 min). The increase in blood flow was unaffected by dexamethasone (1 mg kg −1 , i.v.; −180 min) or indomethacin (10 mg kg −1 , s.c.; −30 min). Hind paw volume was significantly ( P <0.001) increased 30 min after intraplantar peroxynitrite (87.5 and 175 nmol paw −1 ) and remained raised for the duration of the experiment (360 min). By comparison, nociception was not altered by intraplantar peroxynitrite. These data indicate that peroxynitrite can cause an increase in both plasma extravasation and blood flow, suggesting that peroxynitrite could be of biological relevance to microvascular responses. These findings may be of importance in the pathology of inflammatory diseases in which peroxynitrite formation occurs. British Journal of Pharmacology (1997) 122 , 1083–1088; doi: 10.1038/sj.bjp.0701498

It has been suggested in the literature that elevated oxidative protein damage, measured as protein carbonyls, is present in the nervous system of patients with sporadic motor neurone disease (MND). However, the actual reported levels of brain protein carbonyls vary over a wide range. We show here that this is probably due to the use of different protocols for the carbonyl assay; results differ depending on when the dinitrophenylhydrazine reagent is added and at what stage in the procedure protein is assayed for the calculation of carbonyls on a unit protein basis. Using a range of different procedures, we were unable to confirm reports of elevated protein carbonyls in motor cortex from brains of patients with MND. We also measured thiobarbituric acid-reactive material in the brain samples using an HPLC-based TBA test in the presence of butylated hydroxytoluene. In general, there was no significant elevation of TBARS in MND motor cortex. However, four patients showed values higher than any of the control patients (both 'normal' control and 'disease control'). There was no correlation of TBARS with protein carbonyl values. We suggest that oxidative damage in motor cortex in sporadic MND, if it occurs, may be confined to a small group of patients and may affect different molecular targets in each patient.

Abstract Caloric restriction (CR) is one of the most effective interventions to prolong lifespan and promote health. Recently, it has been suggested that hydrogen sulfide (H 2 S) may play a pivotal role in mediating some of these CR-associated benefits. While toxic at high concentrations, H 2 S at lower concentrations can be biologically advantageous. H 2 S levels can be artificially elevated via H 2 S-releasing donor drugs. In this study, we explored the function of a novel, slow-releasing H 2 S donor drug (FW1256) and used it as a tool to investigate H 2 S in the context of CR and as a potential CR mimetic. We show that exposure to FW1256 extends lifespan and promotes health in Caenorhabditis elegans ( C. elegans ) more robustly than some previous H 2 S-releasing compounds, including GYY4137. We looked at the extent to which FW1256 reproduces CR-associated physiological effects in normal-feeding C. elegans . We found that FW1256 promoted healthy longevity to a similar degree as CR but with fewer fitness costs. In contrast to CR, FW1256 actually enhanced overall reproductive capacity and did not reduce adult body length. FW1256 further extended the lifespan of already long-lived eat-2 mutants without further detriments in developmental timing or fertility, but these lifespan and healthspan benefits required H 2 S exposure to begin early in development. Taken together, these observations suggest that FW1256 delivers exogenous H 2 S efficiently and supports a role for H 2 S in mediating longevity benefits of CR. Delivery of H 2 S via FW1256, however, does not mimic CR perfectly, suggesting that the role of H 2 S in CR-associated longevity is likely more complex than previously described.