Induction of apoptosis and absence of inflammation in rat lung after intratracheal instillation of multiwalled carbon nanotubes.

Several studies performed by intratracheal instillation showed that carbon nanotubes (CNT) induced pulmonary fibrosis, granulomas or inflammation. But, recently, two inhalation studies did not observed such pathological phenomena and suggest that granulomas could be due to the instillation of unbreathable agglomerates. In a previous study, we have described a simple method (using albumin as dispersing agent) which produced solutions containing more than 80% of agglomerate of breathable size. We report here results from intratracheal instillation of rats by 0, 1, 10 or 100 microg of MWCNT dispersed with albumin. After 1, 7, 30, 90, and 180 days, inflammation, apoptosis, fibrosis, respiratory parameters and granuloma formation were assessed. Results obtained by plethysmography, soluble collagen quantification, qRT-PCR and luminex measurement of cytokines expression and histopathological observation showed only evidence of apoptosis of alveolar macrophages. These result underline the importance of controlling MWCNT agglomerate size when exposing animals, through appropriate dispersion methods.

Decrease in ovalbumin-induced pulmonary allergic response by benzaldehyde but not acetaldehyde exposure in a Guinea pig model.

The pulmonary effects of two environmentally relevant aldehydes were investigated in nonsensitized or ovalbumin (OA)-sensitized guineapigs (GPs). Four-week-old male Hartley GPs, weighing about 400 g, were intraperitoneally injected with 1 ml of an NaCl solution containing 100 microg OA and 100 mg Al(OH)(3). They were then exposed to either acetaldehyde (200 ppb) or benzaldehyde (500 ppb) for 4 wk (6 h/d, 5 d/wk). At the end of exposure, GPs were challenged with an OA aerosol (0.1% in NaCl) and pulmonary functions were measured. The day after, guinea pigs were anesthetized and several endpoints related to inflammatory and allergic responses were assessed in blood, whole-lung histology, and bronchoalveolar lavage (BAL). Sensitized nonexposed GPs showed bronchial hyperresponsiveness to OA and an increased number of eosinophils in blood and BAL, together with a rise in total protein and leukotrienes (LTB(4) and LTC(4)/D(4)/E(4)) in BAL. In nonsensitized GPs, exposure to acetaldehyde or benzaldehyde did not induce any change in the tested parameters, with the exception of irritation of the respiratory tract as detected by histology and an increased number of alveolar macrophages in animals exposed to acetaldehyde. In sensitized GPs, exposure to acetaldehyde induced a moderate irritation of the respiratory tract but no change in biological parameters linked to the inflammatory and allergic responses. In contrast, exposure to benzaldehyde induced a decrease both in OA-induced bronchoconstriction and in eosinophil and neutrophil numbers in BAL, an increase in the bronchodilatator mediator prostaglandin E(2) (PGE(2)), and a decrease in the bronchoconstrictor mediators LTC(4)/D(4)/E(4). Further investigations are needed to determine if the attenuated response observed in sensitized GPs exposed to benzaldehyde is due to an alteration of the mechanism of sensitization or to a more direct effect on various mechanisms of the allergic response.