Protective effects of N-acetyl-L-cysteine in endotoxemia

Zhang, Haibo; Spapen, Herbert; Nguyen, Duc Nam; Benlabed, Malik; Buurman, Wim A.; Vincent, Jean‐Louis

doi:10.1152/ajpheart.1994.266.5.h1746

Cited by 69 publications

(68 citation statements)

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“…NAC is a membrane-permeable low molecular weight thiol which is thought to have antioxidant properties and to scavenge oxygen-free radicals (Villa & Ghezzi, 1995). Some of the effects of NAC could therefore be related to a potentiation of the effect of NO, by destruction of oxygen-free radicals which are involved in NO breakdown (Zhang et al, 1994). The effects of NAC could also be due to its reaction with NO to form nitrosothiol intermediates which are potent activators of guanyly cyclase (Ignarro et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

Evidence for N‐acetylcysteine‐sensitive nitric oxide storage as dinitrosyl‐iron complexes in lipopolysaccharide‐treated rat aorta

Müller

Kleschyov

Stoclet

1996

British J Pharmacology

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1 The aim of this study was to assess whether or not vasoactive nitric oxide (NO) stores exist within vascular tissue after lipopolysaccharide (LPS)-treatment. 2 Rat thoracic aortic rings (for contraction experiments) or whole thoracic aortae (for electron paramagnetic resonance (e.p.r.) spectroscopy) were incubated for 18 h at 370C in the absence (control) or in the presence of LPS (10 ug ml-'), with or without L-arginine (L-Arg, 1 mM), the substrate of NO synthase (NOS) or Nw-nitro-L-arginine methyl ester (L-NAME, 1 mM), an inhibitor of NOS. 3 Incubation of rat aortic rings with LPS and L-Arg resulted in a significant decrease of the maximum contractile response to noradrenaline (NA, 3 uM). Addition of L-NAME (3 mM) enhanced contraction towards control values. After precontraction with NA and L-NAME, addition of N-acetyl-L-cysteine (NAC, 0.1 to 10 mM) evoked a concentration-dependent relaxation in rings incubated with LPS and LArg, but not in control rings, rings incubated with LPS in the absence of L-Arg or rings incubated with LPS in the presence of L-Arg and L-NAME. Removal of the endothelium did not significantly modify the relaxation induced by NAC. Methylene blue (3 puM), an inhibitor of the activation of guanylyl cyclase by NO, completely abolished the relaxing effect of NAC. 4 The presence of protein-bound dinitrosyl non-haem iron complexes (DNIC) was detected by e.p.r. spectroscopy in aortae incubated with LPS and L-Arg, but not in control aortae. Furthermore in LPStreated aortae, addition of NAC (20 mM) gave rise to the appearance of an e.p.r. signal characteristic of low molecular weight DNIC. 5 These results provide evidence that, within vascular tissue, NO generated from L-Arg by LPS-induced NOS activity can be stored as protein-bound DNIC in non-endothelial cells. Upon addition of NAC, low molecular weight DNIC are released from these storage sites and induce vascular relaxation probably through guanylyl cyclase activation.

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Section: Discussionmentioning

confidence: 99%

Evidence for N‐acetylcysteine‐sensitive nitric oxide storage as dinitrosyl‐iron complexes in lipopolysaccharide‐treated rat aorta

Müller

Kleschyov

Stoclet

1996

British J Pharmacology

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“…Transcriptional regulation is a priority candidate to serum deprivation-induced gene expression. ROS activate NF-κB (Toledano and Leonard, 1991;Baeuerle and Henkel, 1994;Zhang et al, 1994;Flohe et al, 1997;Asehnoune et al, 2004). ROS and other free radicals can also activate AP-1 and NF-κB transcription coordinately (Dhar et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species-Induced Expression of B cell Activating Factor (BAFF) Is Independent of Toll-like Receptor 4 and Myeloid Differentiation Primary Response Gene 88

Kim¹,

Moon²

2009

Biomolecules and Therapeutics

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-Reactive oxygen species play a role in signal transduction and in many human diseases. B-cell activating factor (BAFF) plays a role for mature B cell generation and maintenance and for the incidence of autoimmune diseases. We previously reported that BAFF expression was induced by ROS. In this study, we investigated whether ROS-induced BAFF expression was affected by toll-like receptor (TLR) 4 or myeloid differentiation primary response gene (MyD) 88. BAFF expression was increased by serum deprivation that is an experimental modification to produce ROS. In contrast, TLR4 and MyD88 were decreased by serum deprivation. Although ROS production was decreased in TLR4-nonfunctional or MyD88-deficient splenocytes as compared to that in control mice, serum deprivation increased ROS production and augmented BAFF expression in both cells. 50 μM H2O2 also increased BAFF expression in TLR4-deficient or MyD88-deficient splenocytes. Collectively, results show that BAFF expression may be mediated by TLR4 or MyD88-independent manner and TLR4 or MyD88 may not be required in BAFF expression.

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“…This is thought to play an important role in the development of MOF in critically ill patients [2][3][4]22]. NAC decreases the neutrophil-aggregating activity, enhances nitric oxide release by the endothelium, and has important antioxidant properties [5]. Thus, in theory, NAC may improve O 2 extraction and tissue oxygenation.…”

Section: Discussionmentioning

confidence: 99%

“…A defect in peripheral tissue O 2 extraction can cause covert tissue hypoxia and seems important in the pathogenesis of MOF [2][3][4]. Studies in experimental animals suggest that N-acetylcysteine (NAC) can improve O 2 extraction and tissue oxygenation [5]. In humans, NAC appears to enhance tissue O 2 extraction in patients with fulminant hepatic failure due to acetaminophen overdose [6], but not in patients with sepsis [7].…”

mentioning

confidence: 99%

Effects of N-acetylcysteine on tissue oxygenation in patients with multiple organ failure and evidence of tissue hypoxia

Agustí

Togores²,

Ibáñez³

et al. 1997

Eur Respir J

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Protective effects of N-acetyl-L-cysteine in endotoxemia

Cited by 69 publications

References 0 publications

Evidence for N‐acetylcysteine‐sensitive nitric oxide storage as dinitrosyl‐iron complexes in lipopolysaccharide‐treated rat aorta

Evidence for N‐acetylcysteine‐sensitive nitric oxide storage as dinitrosyl‐iron complexes in lipopolysaccharide‐treated rat aorta

Reactive Oxygen Species-Induced Expression of B cell Activating Factor (BAFF) Is Independent of Toll-like Receptor 4 and Myeloid Differentiation Primary Response Gene 88

Effects of N-acetylcysteine on tissue oxygenation in patients with multiple organ failure and evidence of tissue hypoxia

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