N-Acetylcysteine Inhibits in Vivo Nitric Oxide Production by Inducible Nitric Oxide Synthase

Bergamini, Stefania; Rota, Cristina; Canali, Raffaella; Staffieri, Mariagrazia; Daneri, Francesca; Bini, Anna; Giovannini, Fabiola; Tomasi, Aldo; Iannone, Anna

doi:10.1006/niox.2001.0356

Cited by 81 publications

(47 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…NAC can affect the bioavailability of NO through inhibiting inducible NO synthase activity in vitro (20) and in vivo (21), and/or forming more active NO adducts (22,23). Thus, contradictory observations have been reported on the effects of NAC on NO production during I-R and H-R. Associated with reducing brain injury, NAC has been shown to decrease plasma nitrate-nitrite levels in I-R gerbils (6) as well as NO synthase expression in I-R rats (2).…”

Section: Discussionmentioning

confidence: 99%

Effects of Postresuscitation N-Acetylcysteine on Cerebral Free Radical Production and Perfusion During Reoxygenation of Hypoxic Newborn Piglets

et al. 2008

View full text Add to dashboard Cite

ABSTRACT:Hydrogen peroxide (H 2 O 2 ) and nitric oxide (NO) contribute to the pathogenesis of cerebral hypoxic-ischemic injury. We evaluated the neuroprotective effect of N-acetyl-L-cysteine (NAC, a free radical scavenger) against oxidative stress and perfusion in a model of neonatal hypoxia-reoxygenation (H-R). Piglets (1-3 d, 1.6 -2.3 kg) were randomized into a sham-operated group (without H-R) (n ϭ 5) and two H-R experimental groups (2 h normocapnic alveolar hypoxia followed by 4 h reoxygenation) (n ϭ 7/group). Five minutes after reoxygenation, piglets were given either i.v. saline (H-R controls) or NAC (30 mg/kg bolus then 20 mg/kg/h infusion) in a blinded-randomized fashion. Heart rate, mean arterial pressure, carotid arterial blood flow (transit-time ultrasonic probe), cerebral cortical H 2 O 2 and NO production (electrochemical sensor), cerebral tissue glutathione and nitrotyrosine levels (enzyme-linked immunosorbent assay) were examined. Hypoxic piglets were acidotic (pH 6.88 -6.90), which recovered similarly in the H-R groups (p Ͼ 0.05 versus shams). Postresuscitation NAC treatment significantly attenuated the increase in cortical H 2 O 2 , but not NO, concentration during reoxygenation, with lower cerebral oxidized glutathione levels. NAC-treated piglets had significantly higher carotid oxygen delivery and lower cerebral lactate levels than that of H-R controls with corresponding changes in carotid arterial flow and vascular resistance. In newborn piglets with H-R, postresuscitation administration of NAC reduced cerebral oxidative stress and improved cerebral perfusion. (Pediatr Res 64: 256-261, 2008)

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Postresuscitation N-Acetylcysteine on Cerebral Free Radical Production and Perfusion During Reoxygenation of Hypoxic Newborn Piglets

et al. 2008

View full text Add to dashboard Cite

show abstract

“…There is evidence that NAC decreases concentration of NO through inhibition of inducible NO synthase (iNOS) [48]. The overexpression of iNOS and the subsequent increased generation of NO have been demonstrated in colon biopsies of patients with ulcerative colitis [49] that found to be in relation with disease severity [13,50].…”

Section: Discussionmentioning

confidence: 99%

Molecular evidences on the benefit of N-acetylcysteine in experimental colitis

et al. 2008

View full text Add to dashboard Cite

“…Currently, there is no direct evidence that antioxidant treatments decrease NO in nemertean oocytes by either downregulating NOS activity or scavenging NO, as demonstrated for somatic cells (Bergamini et al 2001, Linares et al 2008, Kim et al 2009, Harput et al 2011. Moreover, even if the antioxidants had been shown to reduce intraoocytic NO, such findings would not preclude the possibility that these broadly acting drugs block GVBD via effects on other targets, including ROS (Nakagawa et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Since each of the tested antioxidants can lower NO levels in somatic cells (Bergamini et al 2001, Linares et al 2008, Kim et al 2009, Harput et al 2011 Figure 1 (A) Antioxidants (aa, ascorbic acid; BHA, butylated hydroxyanisole; gallo, gallotannin; NAC, N-acetylcysteine; tem, tempol) block seawater (SW)-induced GVBD in a dose-dependent manner. (B and C) Conversely, such blockage is reversed after coadding 5 mM of the cAMP elevator forskolin (fors) to 200 mM aa, 500 mM BHA, 100 mM gallo, 150 mM NAC, or 150 mM tem.…”

Section: Role Of No During Gvbdmentioning

confidence: 99%

Inhibition of germinal vesicle breakdown by antioxidants and the roles of signaling pathways related to nitric oxide and cGMP during meiotic resumption in oocytes of a marine worm

Stricker

2012

Reproduction

View full text Add to dashboard Cite

In mammalian oocytes, cAMP elevations prevent the resumption of meiotic maturation and thereby block nuclear disassembly (germinal vesicle breakdown (GVBD)), whereas nitric oxide (NO) and its downstream mediator cGMP can either inhibit or induce GVBD. Alternatively, some invertebrate oocytes use cAMP to stimulate, rather than inhibit, GVBD, and in such cases, the effects of NO/cGMP signaling on GVBD remain unknown. Moreover, potential interactions between NO/cGMP and AMP-activated kinase (AMPK) have not been assessed during GVBD. Thus, this study analyzed intraoocytic signaling pathways related to NO/cGMP in a marine nemertean worm that uses cAMP to induce GVBD. For such tests, follicle-free nemertean oocytes were stimulated to mature by seawater (SW) and cAMP elevators. Based on immunoblots and NO assays of maturing oocytes, SW triggered AMPK deactivation, NO synthase (NOS) phosphorylation, and an NO elevation. Accordingly, SW-induced GVBD was blocked by treatments involving the AMPK agonist AICAR, antioxidants, the NO scavenger carboxy-PTIO, NOS inhibitors, and cGMP antagonists that target the NO-stimulated enzyme, soluble guanylate cyclase (sGC). Conversely, SW solutions combining NO/cGMP antagonists with a cAMP elevator restored GVBD. Similarly, AICAR plus a cAMP-elevating drug reestablished GVBD while deactivating AMPK and phosphorylating NOS. Furthermore, sGC stimulators and 8-Br-cGMP triggered GVBD. Such novel results indicate that NO/cGMP signaling can upregulate SW-induced GVBD and that cAMP-elevating drugs restore GVBD by overriding the inhibition of various NO/cGMP downregulators, including AMPK. Moreover, considering the opposite effects of intraoocytic cAMP in nemerteans vs mammals, these data coincide with previous reports that NO/cGMP signaling blocks GVBD in rats.

show abstract

N-Acetylcysteine Inhibits in Vivo Nitric Oxide Production by Inducible Nitric Oxide Synthase

Cited by 81 publications

References 35 publications

Effects of Postresuscitation N-Acetylcysteine on Cerebral Free Radical Production and Perfusion During Reoxygenation of Hypoxic Newborn Piglets

Effects of Postresuscitation N-Acetylcysteine on Cerebral Free Radical Production and Perfusion During Reoxygenation of Hypoxic Newborn Piglets

Molecular evidences on the benefit of N-acetylcysteine in experimental colitis

Inhibition of germinal vesicle breakdown by antioxidants and the roles of signaling pathways related to nitric oxide and cGMP during meiotic resumption in oocytes of a marine worm

Contact Info

Product

Resources

About