Characterisation of the decomposition behaviour of S-nitrosoglutathione and a new class of analogues: S-Nitrosophytochelatins
ABSTRACT S-Nitrosoglutathione (GSNO) is one of the most abundant S-nitrosothiols present in the body, playing an important role in many important physiological functions. Depletion of GSNO in some pathophysiological conditions makes GSNO a potentially interesting therapeutic molecule. Phytochelatins are glutathione analogues with the following structure: (gamma-glutamyl-cysteine)(n)-glycine. S-Nitroso derivatives of phytochelatins (SNOPCs) carry a greater number of S-nitrosothiol groups per molecule than GSNO and might therefore be very useful as therapeutic agents. The aim of this study was to investigate the in vitro decomposition behaviour of SNOPCs under various physicochemical stress conditions and compare it to the decomposition behaviour of GSNO. SNOPCs were generally less stable than GSNO under all experimental conditions tested, which included exposure to light, variation of pH and temperature as well as exposure to different concentrations of exogenous free thiol in the form of reduced glutathione (GSH). Even under light exclusion at ambient temperature the SNOPCs retained only 40% of their intact SNO groups after a 48h incubation time compared to 90% for GSNO. SNOPCs were also shown to readily take part in transnitrosation reactions when incubated with free glutathione. These properties suggest that SNOPCs could be employed as an investigation tool or possibly as therapeutic agents.
SourceAvailable from: Viswanadha Vijaya Padma[Show abstract] [Hide abstract]
ABSTRACT: Ochratoxin (OTA) is one of the most abundant food contaminating mycotoxins and is commonly present in the food chain. Many of the effects associated with OTA, appear to be mediated through oxidative stress. Although the toxicity of OTA is fairly well characterized, antidotes for alleviating the toxicity are sparsely reported. Dietary antioxidants have gained much importance in the recent years for their antioxidative and therapeutic properties. In the present study the therapeutic strategy was directed towards use of quercetin, a dietary antioxidant to combat OTA-induced toxicity in Vero cell line. Our results demonstrate that quercetin pre-treatment suppressed OTA-induced cytotoxicity and oxidative stress. It modulated OTA-induced alteration on the antioxidant defence through activation of Nrf2 pathway. Morphological studies by scanning electron microscopy (SEM) and cell cycle analysis indicated that quercetin prevented OTA-induced apoptosis. It also inhibited the activation of caspase cascade that leads to DNA fragmentation. Quercetin also exhibited antigenotoxic potential by attenuating OTA-induced DNA damage and micronucleus (MN) formation. The results of the study demonstrate for the first time that quercetin pre-treatment prevents OTA-induced oxidative stress and apoptosis in Vero cell line.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 08/2013; 62. DOI:10.1016/j.fct.2013.08.048 · 2.99 Impact Factor
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ABSTRACT: Construction and biofunctional evaluation of a novel vascular graft with in situ catalytic generation of nitric oxide were described in this paper. Poly α-lysine and poly (γ-glutamic acid) were deposited alternately onto the surface of an electrospun poly ε-caprolactone matrix via electrostatic layer-by-layer self-assembly, and then selenocystamine was loaded as a catalyst. Measurement of in vitro catalytic generation of nitric oxide demonstrated that this catalyst-loaded material could considerably accelerate the release of nitric oxide from S-nitrosoglutathione. A fibroblast proliferation assay showed that the material possessed satisfactory cellular compatibility. The catalyst-loaded material could inhibit the spread of smooth muscle cells in the presence of nitric oxide donors. In arteriovenous-shunt experiment, the catalyst-loaded graft exhibited good anti-thrombotic property where it could prevent acute thrombosis by decreasing the adhesion and activation of platelets and other blood cells. These data suggest a new method of building vascular grafts with improved hemocompatibility and biological functions. Copyright © 2014 Elsevier B.V. All rights reserved.Materials Science and Engineering C 12/2014; 45:491-6. DOI:10.1016/j.msec.2014.09.040 · 2.74 Impact Factor
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ABSTRACT: S-nitrosothiols (RSNO) are considered as potential drugs for delivering nitric oxide ((•)NO) or related species in cardiovascular disorders associated with decrease in (•)NO bioavailability. We have synthesized a new RSNO, i.e. S,S'-dinitrosobucillamine (BUC(NO)2), which combines in its structure two S-mononitrosothiols, S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-N-acetylcysteine (NACNO). Synthesized BUC(NO)2 was structurally characterized using high-performance liquid chromatography/mass spectrometry (HPLC/MS), (1)H nuclear magnetic resonance ((1)H NMR), infrared (IR) and UV-visible spectroscopies, and thermal analysis; resulting data are consistent with the expected structure. The vasorelaxant effect of BUC(NO)2 was evaluated using isolated rat aortic rings and compared to SNAP, NACNO, and to an equimolar mixture of NACNO plus SNAP in order to mimic the number of (•)NO contained in a BUC(NO)2 molecule. BUC(NO)2 (pD2=7.8±0.1) was more potent in vasorelaxation than NACNO (pD2=6.4±0.2), SNAP (pD2=6.7±0.1) and the mixture of SNAP plus NACNO (pD2=6.7±0.2). The release of (•)NO from BUC(NO)2 was 6-fold that of the basal value and significantly higher than the release of (•)NO from the SNAP plus NACNO mixture (4-fold increase versus basal value). Finally, the role of protein disulfide isomerase (PDI) in BUC(NO)2 metabolism was investigated. Vasorelaxant effect (pD2=6.8±0.2) and (•)NO release decreased in the presence of a PDI inhibitor (both P<0.05 versus BUC(NO)2). In conclusion, BUC(NO)2 releases a larger amount of (•)NO into the aorta, partially through PDI activation, and induces vasorelaxation at lower concentrations than other RSNO previously reported.European journal of pharmacology 03/2014; DOI:10.1016/j.ejphar.2014.02.034 · 2.59 Impact Factor