Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits.

Oxidative stress has been implicated in the pathogenesis and progression of chronic obstructive pulmonary disease. Both reactive oxidant species from inhaled cigarette smoke and those endogenously formed by inflammatory cells constitute an increased intrapulmonary oxidant burden. Structural changes to essential components of the lung are caused by oxidative stress, contributing to irreversible damage of both parenchyma and airway walls. In addition, oxidative stress results in alterations in the local immune response, increasing the risk of infections and exacerbations, which, in turn, may accelerate lung function decline. The antioxidant N-acetylcysteine, a glutathione precursor, has been applied in these patients in order to reduce symptoms, exacerbations and the accelerated lung function decline. This article reviews the presently available experimental and clinical data on the antioxidative effects of N-acetylcysteine in chronic obstructive pulmonary disease.

https://erj.ersjournals.com/content/erj/23/4/629.full.pdf

Antioxidant properties of N‐acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease

The role of N-acetylcysteine (NAC) in the treatment of chronic bronchitis is unclear Since a number of studies have been published on this topic, a systematic review of published studies seems justified A systematic search (Medline, Embase, Cochrane Library, bibliographies, no language restriction) for published randomized trials comparing oral NAC with placebo in patients with chronic bronchitis was performed Dichotomous data on prevention of exacerbation, improvement of symptoms and adverse effects were extracted from original reports The relative benefit and number-needed-to-treat were calculated for both individual trials and combined data Thirty-nine trials were retrieved; eleven (2,011 analysed patients), published 1976-1994, were regarded as relevant and valid according to preset criteria In nine studies, 351 of 723 (485%) patients receiving NAC had no exacerbation compared with 229 of 733 (312%) patients receiving placebo (relative benefit 156 (95% confidence interval (CI) 137-177), number-needed-to-treat 58 (95% CI 45-81) There was no evidence of any effect of study period (12-24 weeks) or cumulative dose of NAC on efficacy In five trials, 286 of 466 (614%) patients receiving NAC reported improvement of their symptoms compared with 160 of 462 (346%) patients receiving placebo (relative benefit 178 (95% CI 154-205), number-needed-to-treat 37 (95% CI 30-49)) With NAC, 68 of 666 (102%) patients reported gastrointestinal adverse effects compared with 73 of 671 (109%) taking placebo With NAC, 79 of 1,207 (65%) patients withdrew from the study due to adverse effects, compared with 87 of 1,234 (71%) receiving placebo In conclusion, with treatment periods of approximately 12-24 weeks, oral N-acetylcysteine reduces the risk of exacerbations and improves symptoms in patients with chronic bronchitis compared with placebo, without increasing the risk of adverse effects Whether this benefit is sufficient to justify the routine and long-term use of N-acetylcysteine in all patients with chronic bronchitis should be addressed in further studies and cost-effectiveness analyses

https://erj.ersjournals.com/content/erj/16/2/253.full.pdf

The effect of oral N‐acetylcysteine in chronic bronchitis: a quantitative systematic review

N-acetylcysteine is the acetylated variant of the amino acid L-cysteine and is widely used as the specific antidote for acetaminophen overdose. Other applications for N-acetylcysteine supplementation supported by scientific evidence include prevention of chronic obstructive pulmonary disease exacerbation, prevention of contrast-induced kidney damage during imaging procedures, attenuation of illness from the influenza virus when started before infection, treatment of pulmonary fibrosis, and treatment of infertility in patients with clomiphene-resistant polycystic ovary syndrome. Preliminary studies suggest that N-acetylcysteine may also have a role as a cancer chemopreventive, an adjunct in the eradication of Helicobacter pylori, and prophylaxis of gentamicin-induced hearing loss in patients on renal dialysis.

N-Acetylcysteine: Multiple Clinical Applications

Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid- and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, cu...

Molecular strategies for targeting antioxidants to mitochondria: therapeutic implications.

The results of this general practice study suggest that acetylcysteine (Fabrol) administered orally for 2 months to patients with chronic bronchitis effectively changes the viscosity and character of sputum with resultant ease of expectoration and cough severity. There was a notable improvement in associated abnormal physical signs such as the presence of rhonchi, crepitations and symptoms including dyspnoea at rest. Tolerability was good, with 81% of patients experiencing no side-effects.

Acetylcysteine (Fabrol) in Chronic Bronchitis - A Study in General Practice

The results of this general practice study in 248 patients suggest that acetylcysteine (Fabrol) administered orally for 2 months to patients with chronic bronchitis effectively changes the viscosity and character of sputum with resultant ease of expectoration and cough severity. There was a notable improvement in associated abnormal physical signs such as the presence of rhonchi, crepitations and symptoms including dyspnoea at rest. Tolerability was good, with 77% of patients experiencing no side-effects.

http://journals.sagepub.com/doi/pdf/10.1177/030006058401200206

Irish General Practice Study of Acetylcysteine (Fabrol) in Chronic Bronchitis

This multicentre double-blind trial in general practice compared the efficacy and tolerability of the sustained-release formulation of clomipramine (Anafranil SR) with its conventional formulation (Anafranil) in the treatment of phobias Patients were allocated at random to receive clomipramine 75 mg once daily as either the sustained-release or conventional formulation for 11 weeks following a 1-week dosage build-up period Analysis of results from forty-six patients showed that the sustained release formulation of clomipramine 75 mg was as effective as the conventional formulation of clomipramine 75 mg in improving symptoms of phobia as assessed by a phobia inventory and global evaluation Unwanted effects attributable to therapy were similar in both treatment groups but there were fewer withdrawals due to unwanted effects of the sustained release formulation of clomipramine 75 mg It was concluded that the sustained-release formulation of clomipramine does offer advantages for patients requiring 75 mg clomipramine daily

Efficacy and tolerability of sustained-release clomipramine (Anafranil SR) in the treatment of phobias: a comparison with the conventional formulation of clomipramine (Anafranil).

A Huitson

Papers

Acetylcysteine (Fabrol) in Chronic Bronchitis - A Study in General Practice

Irish General Practice Study of Acetylcysteine (Fabrol) in Chronic Bronchitis

Efficacy and tolerability of sustained-release clomipramine (Anafranil SR) in the treatment of phobias: a comparison with the conventional formulation of clomipramine (Anafranil).