Regular exercise training attenuates pulmonary inflammatory responses to inhaled alumina refinery dust in mice.

Exposure to alumina dust has been recently associated with impaired lung mechanics and inflammation. We aimed at evaluating if moderate exercise training prevents these outcomes. Twenty-three female BALB/c mice (25-30g) were randomly divided in two main groups: control (C) and exercise (E), which were submitted, or not, to 15min of swimming, 5 days/week during 4 weeks. Then, the animals were exposed for 1h to either saline solution (CS or ES) or to a suspension of 8mg/m(3) of alumina dust (CA or EA). Twenty-four hours later pulmonary mechanics was determined by the end-inflation occlusion method. Left lungs were prepared for histology and right lungs for TGF-ß determination. Static elastance increased after alumina dust exposure independently of swimming. In CA group the viscoelastic component of elastance, the viscoelastic/inhomogeneous pressure, the polymorphonuclear amount, the fraction area of alveolar collapse and TGF-ß increased. Thus, exercise training may mitigate the pro-inflammatory response to inhaled aluminum refinery dust.

Antispasmodic effects of a new kaurene diterpene isolated from Croton argyrophylloides on rat airway smooth muscle.

OBJECTIVES: The effects of rel-(1S,4aS,7S,8aS)-7-(1-vinyl)-tetradecahydro-1,4a-dimethylphenanthrene-7,8a-carbolactone-1-carboxylic acid (TCCA), a new ent-kaurene diterpene isolated from Croton argyrophylloides, on rat tracheal preparations were investigated. METHODS: Tracheae were removed and cut into two-cartilage segments that were mounted in organ baths containing Tyrode's solution. RESULTS: TCCA reduced the contractions induced by electrical field stimulation, relaxed K(+)-induced contractions, and inhibited both phasic and tonic components of the K(+)- and ACh-induced contractions. TCCA reduced the serotonin-induced contraction, abolished that evoked by K(+) in the presence of epinephrine, and also reduced the ACh-induced contractions under Ca(2+)-free conditions. TCCA blocked contractions that depend on divalent cation inflow through voltage-operated Ca(2+) channels (VOCCs) and receptor-operated Ca(2+) channels (ROCCs), but had greater potency to block VOCC- than ROCC-dependent contractions or contractions induced by ACh in Ca(2+)-free conditions. TCCA relaxed the phorbol 12,13 dibutyrate (1 µm) induced contraction, but with slight potency. CONCLUSIONS: TCCA induces an antispasmodic effect through several mechanisms including blockade of either VOCCs (with greater potency) or ROCCs, blockade of IP(3)-induced Ca(2+) release from sarcoplasmic reticulum (with intermediate potency) and reduction of the sensitivity of contractile proteins to Ca(2+).

Pulmonary function and histological impairment in mice after acute exposure to aluminum dust.

Along the aluminum refining process, alumina (Al2O3) constitutes the main source of dust. Although aluminum refinery workers present respiratory symptoms with lung functional changes, no conclusive data about lung function impairment after alumina exposure has been so far reported. We examined the pulmonary alterations of exposure to material collected in an aluminum refinery in Brazil. BALB/c mice were exposed in a whole-body chamber for 1 h to either saline (CTRL, n = 11) or to a suspension (in saline) of 8 mg/m(3) of the dust (ALUM, n = 11) both delivered by an ultrasonic nebulizer. Twenty-four hours after exposure lung mechanics were measured by the end-inflation method. Lungs were prepared for histology. ALUM showed significantly higher static elastance (34.61 +/- 5.76 cmH2O/mL), elastic component of viscoelasticity (8.16 +/- 1.20 cmH2O/mL), pressure used to overcome the resistive component of viscoelasticity (1.62 +/- 0.24 cmH2O), and total resistive pressure (2.21 +/- 0.49 cmH2O) than CTRL (27.95 +/- 3.63 cmH2O/mL, 6.12 +/- 0.99 cmH2O/mL, 1.23 +/- 0.19 cmH2O, and 1.68 +/- 0.23 cmH2O, respectively). ALUM also presented significantly higher fraction area of alveolar collapse (69.7 +/- 1.2%) and influx of polymorphonuclear cells (27.5 +/- 1.1%) in lung parenchyma than CTRL (27.2 +/- 1.1% and 14.6 +/- 0.7%, respectively). The composition analysis of the particulate matter showed high concentrations of aluminum. For the first time it was demonstrated in an experimental model that an acute exposure to dust collected in an aluminum producing facility impaired lung mechanics that could be associated with inflammation.