The protective effect of vitamin C, vitamin E and selenium combination therapy on ethanol-induced duodenal mucosal injury

2004 ◽  
Vol 23 (8) ◽  
pp. 391-398 ◽  
Author(s):  
M Koyuturk ◽  
S Bolkent ◽  
S Ozdil ◽  
S Arbak ◽  
R Yanardag
Keyword(s):  
Nitric Oxide ◽  
Vitamin E ◽  
Nitric Oxide Synthase ◽  
Vitamin C ◽  
Protective Effect ◽  
Neuronal Nitric Oxide Synthase ◽  
Mucosal Injury ◽  
The Other ◽  
Absolute Ethanol ◽  
Oxide Synthase

In this study, the effect of a combination of vitamin C, vitamin E and selenium on ethanol-induced duodenal mucosal damage in rats was investigated morphologi-cally and biochemically. The duodenal mucosal injury was produced by oral administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg) and selenium (0.5 mg/kg) for 3 days and absolute ethanol 1 hour after last antioxidant administration and were sacrificed 1 hour after absolute ethanol. Extreme degeneration in intestinal mucosa of rats given ethanol was observed morphologically. In addition, an increase in neuronal nitric oxide synthase immunoreactive areas was observed in the rats of the group given ethanol. On the other hand, a normal morphological appearance and a decrease in neuronal nitric oxide synthase immunoreactive areas were detected in the rats given ethanol+vitamin C+vitamin E+selenium. In the group to which ethanol was administered, an increase in serum cholesterol and a decrease in serum albumin levels were determined. On the other hand, in the group to which ethanol+vitamin C+vitamin E+selenium were administered, serum cholesterol value decreased, and the serum albumin level increased. As a result, we can say that the combination of vitamin C, vitamin E and selenium has a protective effect on ethanolinduced duodenal mucosal injury.

Wie altern Gefäße? Mechanismen und klinische Implikationen

VASA ◽  
2004 ◽  
Vol 33 (1) ◽  
pp. 3-11 ◽  
Author(s):  
van der Loo ◽  
Koppensteiner ◽  
Lüscher
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Vitamin E ◽  
Nitric Oxide Synthase ◽  
Vitamin C ◽  
Oxide Synthase ◽  
Klinische Implikationen

Altern ist ein wichtiger kardialer und vaskulärer Risikofaktor. Für das Gefäßaltern sind genetische, mechanische und hämodynamische Faktoren ausschlaggebend. So sind altersabhängige Veränderungen in Gefäßen, welche weniger Pulsatilität und Blutdruck ausgesetzt sind, wie Kapillaren und Venen, geringer oder abwesend. Vor allem in den großen Widerstandsgefäßen kommt es im Laufe des Alterns morphologisch zu einer Intima- und Mediaverdickung, verknüpft mit einer vermehrten Einlagerung von Matrixsubstanzen, und letztlich resultierend in verminderter Compliance der Gefäße. Es lassen sich Funktionsstörungen des Endothels nachweisen. Hier kommt es zu einer deutlichen Heraufregulierung der endothelialen Nitric Oxide Synthase (eNOS), welche für die Produktion des endogenen Vasodilatators Nitric Oxide (NO) verantwortlich ist. Paradoxerweise sind trotzdem die Vasorelaxationen im Alter vermindert, da es gleichzeitig zu einer erhöhten Produktion freier Radikale, im Besonderen Superoxid (O2-) kommt. O2- und NO bilden in einer schnell ablaufenden chemischen Reaktion Peroxinitrit (ONOO-), welches Proteine nitriert. Durch diese Nitrierung kommt es zur funktionellen Beeinträchtigung dieser Proteine, so dass verschiedene Signalübertragungswege, z.B. Tyrosilierung von Enzymen, blockiert werden. Primärer Ort der Bildung freier Sauerstoffradikale sind die endothelialen Mitochondrien. Bislang ungeklärt ist, ob der oxidative Stress als ein zentrales Ereignis des Gefäßalterns pharmakologisch beeinflussbar ist. Hier standen vor allem antioxidativ wirkende Vitamine im Mittelpunkt des Interesses. Überraschenderweise wird jedoch Vitamin E im Tiermodell vermehrt mit steigendem Alter in der aortalen Wand eingelagert, was im Rahmen eines altersassoziierten gegenregulatorischen Mechanismus zur Abwendung des vermehrten oxidativen Stresses erfolgt. Umgekehrt ist Vitamin C signifikant vermindert. Es bleibt abzuwarten, ob das Gefäßaltern durch Vitamin C oder andere Antioxidantien günstig beeinflusst werden kann. Für Statine und ACE-Hemmer wurden schon Wirkungen beschrieben, die mit Schlüsselmechanismen des Gefäßalterungsprozesses interferieren. Die Entwicklung therapeutischer Interventionen zur Verlangsamung des Gefäßalterns wird für das Auftreten von Herz- und Gefäßerkrankungen im Alter in Zukunft große Bedeutung haben.

scholarly journals PIN/LC8 is associated with cytosolic but not membrane-bound nNOS in the nitrergic varicosities of mice gut: implications for nitrergic neurotransmission

2008 ◽  
Vol 295 (3) ◽  
pp. G442-G451 ◽  
Author(s):  
Arun Chaudhury ◽  
Y. Manjula Rao ◽  
Raj K. Goyal
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
The Other ◽  
Protein Inhibitor ◽  
Sds Page ◽  
Catalytically Active ◽  
Membrane Bound ◽  
Oxide Synthase

This investigation demonstrates the presence and binding of the protein LC8 (described as “protein inhibitor of nNOS” or PIN in some reports) to different components of neuronal nitric oxide synthase (nNOS) in nitrergic varicosities of mice gut. Whole varicosity extracts showed three (320-, 250-, and 155-kDa) nNOS bands with anti-nNOS1422–1433 antibody and a 10-kDa band with anti-LC8 antibody. The LC8 immunoprecipitate (IP) showed three nNOS bands, suggesting that LC8 was bound with all three forms of nNOS but dissociated from them during SDS-PAGE. Studies using LC8 IP and supernatant and probed with anti-CaM showed that LC8 was not associated with CaM-bound 320-kDa nNOS but was present in the CaM-lacking fraction. Probing these fractions with anti-serine847-P-nNOS showed that 320-kDa serine847-phosphorylated-nNOS consisted of LC8-bound and LC8-lacking components. Subsequent studies with varicosity membrane and cytosolic fractions separately showed that membrane contained CaM-bound and CaM-lacking, serine847-phosphorylated 320-kDa nNOS; both these fractions lacked LC8. On the other hand, the cytosolic fraction contained CaM-lacking, serine847-phosphorylated 320-kDa, 250-kDa, and 155-kDa nNOS bands that were all associated with LC8. These studies, along with in vitro nitric oxide assays, show that in gut nitrergic nerve varicosities 1) all cytosolic serine847-phosphorylated nNOS was catalytically inactive and bound with LC8, and 2) membrane-associated nNOS consisted of catalytically active, CaM-bound and catalytically inactive, CaM-lacking, serine847-phosphorylated nNOSα dimers, both of which lacked LC8. These results suggest that LC8 may dissociate from the 320-kDa nNOSα dimer upon binding to membrane, thus supporting the view that LC8 may transport nNOSα dimer to the varicosity membrane for participation in nitrergic neurotransmission.

scholarly journals Effects of pH on the structure and function of neuronal nitric oxide synthase

1998 ◽  
Vol 331 (3) ◽  
pp. 801-807 ◽  
Author(s):  
Antonius C. F. GORREN ◽  
Astrid SCHRAMMEL ◽  
Kurt SCHMIDT ◽  
Bernd MAYER
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
High Spin ◽  
Spin State ◽  
Neuronal Nitric Oxide Synthase ◽  
Low Ph ◽  
The Other ◽  
Binding Studies ◽  
Nadph Oxidation ◽  
Oxide Synthase

We investigated how pH affects rat brain neuronal nitric oxide synthase (nNOS) with regard to spin-state equilibrium and the thiolate ligand bond of the haem group, catalytic activity, and monomer ↔ dimer equilibrium. At neutral pH, nNOS containing 1 equiv. of (6R)-5,6,7,8-tetrahydro-l-biopterin (BH4) per dimer was mostly high-spin (λmax at 398 nm), whereas the BH4-free enzyme consisted of a mixture of the high-spin and two low-spin forms (λmax at 418 nm, and at 376 and 456 nm respectively). With BH4-free nNOS, an appreciable high-spin fraction was only observed between pH 7 and 8; at pH 6 and 9, the 418 and 376/456 nm low-spin forms predominated respectively. With nNOS containing 1 equiv. of BH4 per dimer, similar observations were made, but these involved only half of the enzyme; the other half, presumably the BH4-containing subunits, remained high-spin. Since the spin state in the BH4-free subunit appeared little affected by the state of the other subunit, we conclude that, in dimeric nNOS, the two haem groups function independently. Low pH destabilized thiolate binding and the interaction between NOS subunits, as indicated by CO-binding studies and gel electrophoresis respectively. Formation of l-citrulline was optimal between pH 7.0 and 7.5; the decrease in NOS activity at lower pH proved to be due to uncoupling of NADPH oxidation, resulting in increased formation of H2O2. At high pH strict coupling of l-arginine and NADPH oxidation was maintained, even in the absence of exogenous BH4. The possible pathophysiological implications of the uncoupling at low pH are discussed.

β-Adrenoceptor and nNOS-derived NO interactions modulate hypoglycemic pial arteriolar dilation in rats

2001 ◽  
Vol 280 (2) ◽  
pp. H562-H568 ◽  
Author(s):  
Roberto A. Santizo ◽  
Heidi M. Koenig ◽  
Dale A. Pelligrino
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Topical Application ◽  
Plasma Glucose ◽  
Neuronal Nitric Oxide Synthase ◽  
The Other ◽  
Neuronal Transmission ◽  
Oxide Synthase ◽  
Arteriolar Diameter ◽  
Nnos Inhibition

We examined the relative contributions from nitric oxide (NO) and catecholaminergic pathways in promoting cerebral arteriolar dilation during hypoglycemia (plasma glucose ≅ 1.4 mM). To that end, we monitored the effects of β-adrenoceptor (β-AR) blockade with propranolol (Pro, 1.5 mg/kg iv), neuronal nitric oxide synthase (nNOS) inhibition with 7-nitroindazole (7-NI, 40 mg/kg ip) or ARR-17477 (300 μM, via topical application), or combined intravenous Pro + 7-NI or ARR-17477 on pial arteriolar diameter changes in anesthetized rats subjected to insulin-induced hypoglycemia. Additional experiments, employing topically applied TTX (1 μM), addressed the possibility that the pial arteriolar response to hypoglycemia required neuronal transmission. Separately, Pro and 7-NI elicited modest but statistically insignificant 10–20% reductions in the normal ∼40% increase in arteriolar diameter accompanying hypoglycemia. However, combined Pro-7-NI was accompanied by a >80% reduction in the hypoglycemia-induced dilation. On the other hand, the combination of intravenous Pro and topical ARR-17477 did not affect the hypoglycemia response. In the presence of TTX, the pial arteriolar response to hypoglycemia was lost completely. These results suggest that 1) β-ARs and nNOS-derived NO interact in contributing to hypoglycemia-induced pial arteriolar dilation; 2) the interaction does not occur in the vicinity of the arteriole; and 3) the vasodilating signal is transmitted via a neuronal pathway.

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