N-acetylcysteine prevents cigarette smoke induced small airways alterations in rats

Abstract

This study investigated the effect of cigarette smoke exposure and the potential protection N-acetylcysteine (NAC) in rat lungs.Forty-eight rats were exposed to cigarette smoke (CS) for 10 weeks, without (CS group) or with (CS+NAC group) oral intake of NAC 200 mg . rat -1 . day -1 , or to fresh air (Control). All rat lungs were assessed in terms of lung function, ventilation distribution (nitrogen, helium and sulphur hexafluoride phase III slopes), and morphometry (airway wall thickening of small, medium and large bronchi).The small bronchi, defined as the airways with an internal perimeter <1,000 mm showed significantly thicker airway walls in the CS than in the Control group. By contrast, no airway wall thickening was observed in the CS+NAC group with respect to Control. Except for decreased lung volumes and compliance in CS and CS+NAC groups, which were entirely attributable to smaller body weight gain, lung function was indistinguishable from Control. Phase III slopes were significantly increased only in the CS group.In conclusion, smoke-induced alterations in the rat lungs were reflected in wall thickening of the small bronchi and increased ventilation maldistribution. These smoke-induced morphometric and ventilation distribution alterations were prevented by N-acetylcysteine. Eur Respir J 2000; 15: 505±511. In humans, a major site of inflammatory action of cigarette smoke has been attributed to the so-called small airways, stimulating a number of studies aimed at characterizing and detecting structural change in the lung periphery [1,2]. The phase III slope of the N 2 single breath washout (SBW) test became a popular index of small airways alteration since the work by COSIO et al. [3] showed its correlation with morphological scores of small airways abnormalities in smokers with normal spirometry. A later SBW study by VAN MUYLEM et al. [4], which included helium and sulphur hexafluoride tracer concentrations, also revealed distinct correlations between indices derived from He and SF 6 slopes and airway pathology scores. Due to the fact that the diffusion front is located more peripherally for SF 6 than for He, the respective phase III slopes are indicative of the site where ventilation inhomogeneities occur.Although animal studies are well-suited for the study of lung function in the diseased lung, the difficulty often resides in reproducing a lesion which is comparable to that encountered in the human lung [5]. Previous studies in rats have led to conflicting results as to whether the cigarette smoke induces emphysematous lesions [6,7] or not [8,9] and not all studies provide any information about the extent to which the nonalveolated airways are affected [10]. Despite these difficulties, rat lungs have been used to investigate the possible protective role of N-acetylcysteine (NAC) over cigarette smoke induced lesions. NAC is an antioxidant and can therefore be expected to change lung oxidant-antioxidant imbalance induced by cigarette smoke which is a source of oxidants. Previous histopathology...

Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats

“…The ability of NAC to reduce the increased number of mucus secretory cells in airway epithelium and the upregulation of Muc5ac in the bleomycin model of lung fibrosis has been demonstrated. This finding is in keeping with previous data for NAC preventing the goblet cell hyperplasia [19], mucus hypersecretion [28] and morphometric and ventilation alterations [29] in a rat model, or bronchitis produced by cigarette smoke exposure as well as the enhanced expression of Muc5ac in sensitised rats after allergen challenge [30]. These observations indicate that the activity of NAC in different models of lung inflammation is not merely related to its mucolytic properties, since its antioxidant properties may also influence the intracellular signalling involved in mucus secretion.…”

Comprehensive gene expression profiling of rat lung reveals distinct acute and chronic responses to cigarette smoke inhalation

“…There has previously only been one other report that we know of demonstrating a change in airway collagen in rats in response to CS exposure (30). The increase in airway collagen was no longer significant at 34 wk due to the increased level of collagen in the air-exposed controls.…”

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

“…Treatment with NAC also attenuated rat secretory cell hyperplasia induced by tobacco smoke [58] and prevented hypochlorous acid-mediated inactivation of a 1 -PI in vitro [59]. In a rat model of cigarette smoke-induced alterations in small airways, NAC prevented thickening of the airway wall and improved distribution of ventilation [60].…”