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Nitric Oxide Formation (nitric + oxide_formation)
Selected AbstractsGRAPE SEED PROANTHOCYANIDIN EXTRACT CHELATES IRON AND ATTENUATES THE TOXIC EFFECTS OF 6-HYDROXYDOPAMINE: IMPLICATIONS FOR PARKINSON'S DISEASEJOURNAL OF FOOD BIOCHEMISTRY, Issue 2 2010TZU-HUA WU ABSTRACT Proanthocyanidins are potent antioxidants associated with protection against diseases. We tested the reducing capacity, iron chelating activity, and anti-auto-oxidation ability of grape seed proanthocyanidin extract (GSPE). The mechanisms underlying GSPE attenuation of oxidative processes induced by 6-hydroxydopamine (6-OHDA), a neurotoxin used to induce Parkinson's disease, were investigated in cell-based systems. At high concentrations, GSPE (50 µg/µL) was a mild pro-oxidant in a Fenton-type reaction. GSPE (300 µg/mL) was as potent as 30 µM deferoxamine in its iron-chelating capacity, and as efficient as 5 mM ascorbic acid in delaying 6-OHDA auto-oxidation. In PC-12 cell cultures, 100 and 300 µg/mL GSPE significantly protected (P < 0.05) cells from 6-OHDA-induced (400 µM) toxicity. GSPE-induced cytoprotection is enhanced by a nitric oxide synthase inhibitor (NOSI), implying that the cytoprotective effect of GSPE does not require NOS activation. In conclusion, the iron-chelating activity of GSPE minimizes its pro-oxidant activity and delays 6-OHDA auto-oxidation to provide cytoprotection. PRACTICAL APPLICATIONS Parkinson's disease is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons. The recognized pharmacological strategies to prevent or treat Parkinson's disease include the minimization of oxidative stress, iron release and excitotoxicity resulting from excess nitric oxide formation. One of the best ways to delay or prevent the onset of the disease is to improve the biological antioxidant status by providing additional radical scavengers that are not pro-oxidants. The pro-oxidant activity, such as that of the antioxidant ascorbic acid, enhances radical cycling under certain conditions, and therefore may be detrimental. Grape seed proanthocyanidin extracts (GSPEs) are used as a dietary supplement in food products in several countries. Our current report provides evidence that GSPE has limited pro-oxidant activity, presumably because of its iron-chelating abilities, and protects cells from neurotoxic insults. GSPE may be effective as a dietary supplement for prophylactic use against the progressive neurodegeneration seen in Parkinson's disease. [source] Neuroprotection by melatonin from glutamate-induced excitotoxicity during development of the cerebellum in the chick embryoJOURNAL OF PINEAL RESEARCH, Issue 2 2000Auxiliadora Espinar This work investigated the ability of melatonin to prevent cell damage in the cerebellar cortex of chick embryo caused by glutamate administration. Cell injury was evaluated estimating, at ultrastructural level, the phenomenon of cell death and the synaptogenesis of the Purkinje cells and the cerebellar glomerular synaptic complex. Administration of glutamate during cerebellar development of the chick provokes excitotoxic neuronal degeneration characterized by a phenomenon of neuronal cell death that exhibits essentially the features of a death pattern described as necrosis and the deletion of synaptogenic processes. Our results show that melatonin has a neuroprotective effect against glutamate-induced excitotoxicity. This effect is morphologically revealed by the lack of neural cell death in the embryos treated with melatonin prior to glutamate injection and also by the degree of a synaptogenesis similar to that exhibited by the control group. Likewise, we corroborate the absence of teratological effects of melatonin on chick cerebellar development. Although the possible mechanisms involved in the neuroprotective effect of melatonin are discussed, i.e., direct antioxidant effects, up-regulating endogenous antioxidant defenses, and inhibiting nitric oxide formation activated by glutamate, further studies are required to establish the actual mechanism involved in the neuroprotective effect of melatonin. [source] Extracellular Arginine Rapidly Dilates In Vivo Intestinal Arteries and Arterioles Through a Nitric Oxide MechanismMICROCIRCULATION, Issue 2 2008Laura Pezzuto ABSTRACT Objective: Arginine used for nitric oxide formation can be from intracellular stores or transported into cells. The study evaluated the rapidity, and primary site of NO and vascular resistance responses to arginine at near physiological concentrations (100,400 , M). Methods: Arginine was applied to a single arteriole through a micropipette to determine the fastest possible responses. For vascular blood flow and [NO] responses, arginine was added to the bathing media. Results: Dilation of single arterioles to arginine began in 10,15 seconds and application over the entire vasculature increased [NO] in , 60,90 seconds, and flow increased within 120,300 seconds. Resting periarteriolar [NO] for arterioles was 493.6 ± 30.5 nM and increased to 696.1 ± 68.2 and 820.1 ± 110.5 nM at 200 and 400 , M L-arginine. The blood flow increased 50% at 400,1200 , M L-arginine. The reduced arterial resistance during topical arginine was significantly greater than microvascular resistance at 100 and 200 , M arginine. All responses were blocked by L-NAME. Conclusions: This study demonstrated arterial resistance responses are as or more responsive to arginine induced NO formation as arterioles at near physiological concentrations of arginine. The vascular NO and resistance responses occurred rapidly at L-arginine concentrations at and below 400 , M, which predict arginine transport processes were involved. [source] Suppressive effect of inducible nitric oxide synthase (iNOS) expression by the methanol extract of Actinodaphne lancifoliaPHYTOTHERAPY RESEARCH, Issue 10 2004Youngleem Kim Abstract Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) has played a crucial role in various pathophysiological processes including in,ammation and carcinogenesis. Therefore, the inhibitors of NO synthesis or iNOS gene expression have been considered as potential anti-in,ammatory and cancer chemopreventive agents. In our continuous search for iNOS inhibitors from natural products we have evaluated indigenous Korean plant extracts using an assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. As a result, the methanolic stem extract of Actinodaphne lancifolia showed an inhibitory activity of NO production in a dose-dependent manner (IC50 = 2.5 µg/ml). Additional study demonstrated that the extract of Actinodaphne lancifolia signi,cantly suppressed the iNOS protein and gene expression in a dose-dependent manner. These results suggest that Actinodaphne lancifolia could be a potential candidate for developing an iNOS inhibitor from natural products. Further elucidation of active principles for development of new cancer chemopreventive and/or anti-in,ammatory agents could be warranted. Copyright © 2004 John Wiley & Sons, Ltd. [source] Effects of a high-fat meal on resistance vessel reactivity and on indicators of oxidative stress in healthy volunteersCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 4 2001Andreas Schinkovitz High fat meals postprandially impair macrovascular endothelial function and a link to increased oxidative stress is suggested. Few information, on the other hand, exists on the effect of postprandial hyperlipidaemia on resistance vessel function. Under normal circumstances this vascular bed regulates tissue perfusion and, by controlling flow, impacts on macrovascular nitric oxide formation. The impact of a high fat meal (1200 kcal, 90 g fat, 46 g protein and 47 g carbohydrates) on postprandial resistance vessel reactivity and on indicators of oxidative stress was studied in 11 healthy subjects by venous-occlusion plethysmography using another six subjects as time control group. Ingestion of the test meal resulted in a pronounced increase of serum triglycerides from 1·05 ± 0·61 mmol l,1 in the fasting state to peak postprandial values of 1·94 ± 0·41 mmol l,1 (P < 0·001) reached after 4 h and a return to baseline after 8 h. Fasting peak reactive hyperaemia (RH) was 19·6 ± 2·4 ml min,1 (100 ml),1. Two hours after ingestion of the test meal peak RH was transiently reduced to 16·8 ± 2·2 ml min,1 (100 ml),1 (P < 0·05). No alteration of resting forearm perfusion was observed. The time course of peak RH suggested a potential biphasic effect of the test meal with an early impairment and a late increase of RH. Ingestion of a lipid rich test meal did not exert any influence on either total plasma antioxidant capacity given in trolox equivalents (513 ± 26 ,mol l,1 at baseline) or on plasma peroxides measured as H2O2 equivalents (469 ± 117 ,mol l,1). Our results suggest that ingestion of a meal containing 90 g of fat results in a transient impairment of reactive hyperaemia in healthy subjects but these vascular alterations are not accompanied by signs of systemically increased oxidative stress. [source] | ||||||||||