Intravenous Administration of N-Acetylcysteine

Crouch, Barbara Insley; Rusho, William J.

doi:10.1016/j.annemergmed.2005.02.027

Cited by 7 publications

(7 citation statements)

References 2 publications

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“…NAC when orally administered is metabolized into another compounds since accompanying increase in non-protein and protein sulphydryl groups were found in plasma (Cotgreave et al, 1987; De Caro et al, 1989). It is important to note that increasing the dose also increased NAC bioavailability and time for maximal plasma concentration (Borgstrom and Kagedal, 1990) and higher concentration in plasma may be achieved after intravenous administration (Crouch and Rusho, 2005). The volume of distribution ranges from 0.33 to 0.47 L/kg and protein binding is significant, reaching approximately 50% 4 hours post-administration (Holdiness, 1991).…”

Section: Therapies/clinical Trials With Gsh Analogsmentioning

confidence: 99%

Environmental toxicity, redox signaling and lung inflammation: The role of glutathione

Biswas

Rahman

2009

Molecular Aspects of Medicine

292

198

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Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is the most abundant intracellular antioxidant thiol and is central to redox defense during oxidative stress. GSH metabolism is tightly regulated and has been implicated in redox signaling and also in protection against environmental oxidant-mediated injury. Changes in the ratio of the reduced and disulfide form (GSH/GSSG) can affect signaling pathways that participate in a broad array of physiological responses from cell proliferation, autophagy and apoptosis to gene expression that involve H2O2 as a second messenger. Oxidative stress due to oxidant/antioxidant imbalance and also due to environmental oxidants is an important component during inflammation and respiratory diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and asthma. It is known to activate multiple stress kinase pathways and redox sensitive transcription factors such as Nrf2, NF-κB and AP-1, which differentially regulate the genes for pro-inflammatory cytokines as well as the protective antioxidant genes. Understanding the regulatory mechanisms for the induction of antioxidants, such as GSH, versus pro-inflammatory mediators at sites of oxidant-directed injuries may allow for the development of novel therapies which will allow pharmacological manipulation GSH synthesis during inflammation and oxidative injury. This article features the current knowledge about the role of GSH in redox signaling, GSH biosynthesis and particularly the regulation of transcription factor Nrf2 by GSH and downstream signaling during oxidative stress and inflammation in various pulmonary diseases. We also discussed the current therapeutic clinical trials using GSH and other thiol compounds, such as N-acetyl-L-cysteine, fudosteine, carbocysteine, erdosteine in environment-induced airways disease.

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Section: Therapies/clinical Trials With Gsh Analogsmentioning

confidence: 99%

Environmental toxicity, redox signaling and lung inflammation: The role of glutathione

Biswas

Rahman

2009

Molecular Aspects of Medicine

292

198

View full text Add to dashboard Cite

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“…The oral availability of NAC varied between 6 and 10% in man [Borgstrom et al 1984]. It is important to note that increasing the dose also increased NAC bioavailability and time for maximal plasma concentration [Borgstrom and Kagedal 1990], still higher concentration in plasma may be achieved after intravenous administration [Crouch and Rusho 2005]. Ongoing clinical trials with NAC in these patients suggest that this thiol compound is well tolerated and may increase pulmonary levels of GSH.…”

Section: Therapeutic Antioxidant Agentsmentioning

confidence: 99%

Review: Antioxidant therapeutic advances in COPD

Rahman

2008

Ther Adv Respir Dis

118

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Chronic obstructive pulmonary disease (COPD) is associated with high incidence of morbidity and mortality. Oxidative stress is intimately associated with the progression and exacerbation of COPD and therefore targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to have beneficial outcome in the treatment of COPD. Among the various antioxidants tried so far, thiol antioxidants and mucolytic agents, such as glutathione, N-acetyl-Lcysteine, N-acystelyn, erdosteine, fudosteine, and carbocysteine; Nrf2 activators, and dietary polyphenols (curcumin, resveratrol, green tea, and catechins/quercetin) have been reported to increase intracellular thiol status alongwith induction of GSH biosynthesis. Such an elevation in the thiol status in turn leads to detoxification of free radicals and oxidants as well as inhibition of ongoing inflammatory responses. In addition, specific spin traps, such as a-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo in the lung. Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of COPD; it is possible that therapeutic administration of multiple antioxidants and mucolytics will be effective in management of COPD. However, a successful outcome will critically depend upon the choice of antioxidant therapy for a particular clinical phenotype of COPD, whose pathophysiology should be first properly understood. This article will review the various approaches adopted to enhance lung antioxidant levels, antioxidant therapeutic advances and recent past clinical trials of antioxidant compounds in COPD. KeywordsCOPD; Smokers; Oxidants; Thiol; Glutathione; Antioxidants; Lungs Oxidative stress in COPD COPD and inhaled oxidantsThe lung is exposed to a high-oxygen environment and exogenous pollutants/toxicants that come along with the inhaled breath. Considering its large surface area and associated blood supply, the lung is therefore highly susceptible to injury mediated by oxidative stress. Oxidative stress is a consequence of an inability of resident antioxidant mechanisms to neutralize prooxidant factors generated endo-or exogenously. Reactive oxygen and nitrogen species (ROS and RNS) are the most prominent manifestations of oxidative stress and are associated with remodeling of extracellular matrix and blood vessels, elevated mucus secretion, [Janssen-Heininger et al. 2002;Rahman and MacNee 1998; (Figure 1). Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD) it is possible that therapeutic administration of appropriate antioxidants will be effective in the treatment of COPD [Rahman 2002;. Given the existence of various clinical phenotypes of COPD [Patel et al. 2006;Makita et al. 2007], it becomes important to understand, which particular type ...

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“…Diğer hastaların tamamının acil servisten şifa ile taburcu olduğu belirlendi. (13,16,17). İki prospektif çalışmada bu yan etkilerin oranları %42 ve %48 iken, üç retrospektif çalışmada ise bu oranlar %3.7 ile %9 arasında değişmektedir (18)(19)(20)(21)(22).…”

Section: Gereç Ve Yöntemunclassified