Acrolein-induced oxidative and nitrosative stress and its impact on respiratory mechanics in mice assessed using the forced oscillation technique

Acrolein exposure in the lung was studied to determine the effect of acrolein on airway responsiveness and pulmonary mechanics, as measured by the forced oscillation technique (FOT), under conditions of airway activation by methacholine (MCh), as well as with no activation, using the negative pressure-driven forced expiratory (NPFE) maneuvers to assess quasi-static lung compliance. Direct intratracheal acrolein was applied to C57BL/6 J male mice in dosages of 0 (saline vehicle-only) or 4 mg/kg, with FOT and NPFE assessments made 48 hr post-acrolein administration. Our results suggest that lipid peroxidation may be a primary factor in the observed attenuated response of resistance of the respiratory system (Rrs) to MCh (25 % decrease), potentially due to the alteration of the lipid bilayer that contains the transmembrane muscarinic receptors that respond to MCh. Furthermore, static lung compliance was significantly reduced in mice receiving acrolein. The product of lipid peroxidation, malondialdehyde (MDA), was confirmed in the bronchoalveolar lavage fluid (BALF) of the acrolein group to be significantly higher than the control groups (35 % increase). The nitrite concentration measured in the acrolein group BALF was consistent with elevated levels of nitric oxide (NO) (∼50 % increase), and perhaps peroxynitrite, which could be additional nitrosative stress factors promoting lipid peroxidation in our acute model of acrolein toxicity. Furthermore, the decrease in glutathione peroxidase (GPx) (52 % decrease) that we observed suggested a significant reduction in endogenous antioxidant capacity, with the oxidative stress associated with increased lipid peroxidation resultant from acrolein exposure. We conclude that the lipid peroxidation and decline in redox capacity due to nitrosative stress induced by acrolein could be an important factor in modulation of pulmonary mechanics, airway remodeling, and bronchial responsiveness.