Journal ArticleDOI
Low-dose N-Acetylcysteine Protects Rats against Endotoxin-mediated Oxidative Stress, But High-dose Increases Mortality
R. C. Sprong,A. M. L. Winkelhuyzen-Janssen,C. J. M. Aarsman,J. F. L. M. Van Oirschot,T. van der Bruggen,B. S. Van Asbeck +5 more
TLDR
It is concluded that low-dose NAC protects against LPS toxicity by scavenging H2O2, while higher doses may have the opposite effect.Abstract:
We evaluated the effect of the antioxidant N-acetylcysteine (NAC) on oxidative stress, lung damage, and mortality induced by an endotoxin (lipopolysaccharide, or LPS) in the rat. Continuous intravenous infusion of 275 mg NAC/kg in 48 h, starting 24 h before LPS challenge, decreased hydrogen peroxide (H2O2) concentrations in whole blood (p < 0.01). This decrease was accompanied by fewer histologic abnormalities of the lung and decreased mortality (p < 0.025), compared with rats receiving LPS alone. N-Acetylserine, which has no sulfhydryl group, did not protect rats against LPS toxicity. Improved survival was not associated with an increase in pulmonary reduced glutathione, nor with inhibition of serum tumor necrosis factor (TNF) activity. In vitro, TNF production and DNA binding of nuclear factor kappa B (NF-kappaB) in human Mono Mac 6 cells was only inhibited at concentrations of NAC above 20 mM. High-dose NAC treatment (550 and 950 mg/kg in 48 h) decreased lung GSH (p < 0.05) and resulted in a significantly smaller number of surviving animals when compared with the low-dose NAC group (p < 0.025). In vitro, NAC increased hydroxyl radical generation in a system with Fe(III)-citrate and H2O2 by reducing ferric iron to its catalytic, active Fe2+ form. We conclude that low-dose NAC protects against LPS toxicity by scavenging H2O2, while higher doses may have the opposite effect.read more
Citations
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Journal ArticleDOI
Genetic, biochemical, and clinical features of chronic granulomatous disease
TL;DR: The reduced nicotinamide dinucleotide phosphate (NADPH) oxidase complex allows phagocytes to rapidly convert O2 to superoxide anion which then generates other antimicrobial reactive oxygen intermediates, such as H2O2, hydroxyl anion, and peroxynitrite anion.
Journal ArticleDOI
The chemistry and biological activities of N-acetylcysteine
TL;DR: The present review is focused on the chemistry of NAC and its interactions and functions at the organ, tissue and cellular levels in an attempt to bridge the gap between its recognized biological activities and chemistry.
Journal ArticleDOI
Lung glutathione and oxidative stress: implications in cigarette smoke-induced airway disease
Irfan Rahman,William MacNee +1 more
TL;DR: Knowledge of the mechanisms of GSH regulation in the lungs could lead to the development of novel therapies based on the pharmacological or genetic manipulation of the production of this important antioxidant in lung inflammation and injury.
Journal ArticleDOI
Interplay of IKK/NF-κB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy
Swarnali Acharyya,S. Armando Villalta,Nadine Bakkar,Tepmanas Bupha-Intr,Paul M.L. Janssen,Micheal Carathers,Zhi-Wei Li,Amer A. Beg,Sankar Ghosh,Zarife Sahenk,Michael Weinstein,Katherine L. Gardner,Jill A. Rafael-Fortney,Michael Karin,James G. Tidball,Albert S. Baldwin,Denis C. Guttridge +16 more
TL;DR: It is suggested that the IKK/NF-kappaB signaling pathway as a potential therapeutic target for DMD and specific pharmacological inhibition of IKK resulted in improved pathology and muscle function in mdx mice.
Journal ArticleDOI
Nuclear factor kappa B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy.
TL;DR: Therapeutic interventions aimed at limiting NF-kappaB activation and down-regulating production of inflammatory mediators could prove to be beneficial in decreasing host-derived tissue injury and organ dysfunction.
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