Effects of oleanolic acid on pulmonary morphofunctional and biochemical variables in experimental acute lung injury.

We analysed the effects of oleanolic acid (OA) on lung mechanics and histology and its possible mechanisms of action in experimental acute lung injury (ALI). BALB/c mice were randomly divided into Control (saline, ip) and ALI (paraquat, 25 mg/kg, ip) groups. At 1 h, both groups were treated with saline (SAL, 50 µl ip), OA (10 mg/kg ip), or dexamethasone (DEXA, 1 mg/kg ip). At 24 h, lung static elastance, viscoelastic pressure, and alveolar collapse reduced more after OA compared to DEXA administration. Tumour necrosis factor-α, macrophage migration inhibitory factor, interleukin-6, interferon-γ, and transforming growth factor-ß mRNA expressions in lung tissue diminished similarly after OA or DEXA. Conversely, only OA avoided reactive oxygen species generation and yielded a significant decrease in nitrite concentration. OA and DEXA restored the reduced glutathione/oxidized glutathione ratio and catalase activity while increasing glutathione peroxidase induced by paraquat. In conclusion, OA improved lung morphofunction by modulating the release of inflammatory mediators and oxidative stress.

Different strains of mice present distinct lung tissue mechanics and extracellular matrix composition in a model of chronic allergic asthma.

The impact of genetic factors on asthma is well recognized but poorly understood. We tested the hypothesis that different mouse strains present different lung tissue strip mechanics in a model of chronic allergic asthma and that these mechanical differences may be potentially related to changes of extracellular matrix composition and/or contractile elements in lung parenchyma. Oscillatory mechanics were analysed before and after acetylcholine (ACh) in C57BL/10, BALB/c, and A/J mice, subjected or not to ovalbumin sensitization and challenge. In controls, tissue elastance (E) and resistance (R), collagen and elastic fibres' content, and alpha-actin were higher in A/J compared to BALB/c mice, which, in turn, were more elevated than in C57BL/10. A similar response pattern was observed in ovalbumin-challenged animals irrespective of mouse strain. E and R augmented more in ovalbumin-challenged A/J [E: 22%, R: 18%] than C57BL/10 mice [E: 9.4%, R: 11%] after ACh In conclusion, lung parenchyma remodelled differently yielding distinct in vitro mechanics according to mouse strain.

Oral tolerance attenuates airway inflammation and remodeling in a model of chronic pulmonary allergic inflammation.

We investigated the effects of oral tolerance (OT) in controlling inflammatory response, hyperresponsiveness and airway remodeling in guinea pigs (GP) with chronic allergic inflammation. Animals received seven inhalations of ovalbumin (1-5mg/mL-OVA group) or normal saline (NS group). OT was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st ovalbumin inhalation (OT1 group) or after the 4th (OT2 group). The induction of OT in sensitized animals decreased the elastance of respiratory system (Ers) response after both antigen and methacholine challenges, peribronchial edema formation, eosinophilic airway infiltration, eosinophilopoiesis, and airways collagen and elastic fiber content compared to OVA group (P<0.05). The number of mononuclear cells and resistance of respiratory system (Rrs) responses after antigen and methacholine challenges were decreased only in OT2 group compared to OVA group (P<0.05). Concluding, our results show that inducing OT attenuates airway remodeling as well as eosinophilic inflammation and respiratory system mechanics.

Respiratory effects of lipopolysaccharide-induced inflammatory lung injury in mice.

The pathogenic mechanisms of lipopolysaccharide (LPS)-induced lung injury have not been classified. This study examined the physiological changes after endotoxin inhalation and related those to features of pulmonary inflammation in mice. Pulmonary mechanics, histopathology, and bronchoalveolar lavage fluid (BALF) from BALB/c mice were analysed at different occasions (3, 24, 48 and 72 h) after inhalation of saline or LPS from Escherichia coli (0.3 (L0.3) or 10 mg x mL(-1) (L10)). Mice were sedated, anaesthetized, and ventilated. After chest wall resection static (Est) and dynamic (Edyn) elastances, deltaE (Edyn-Est), resistive (deltaP1) and viscoelastic/inhomogeneous pressures (deltaP2), and deltaP1+deltaP2 (deltaPtot) were obtained by end-inflation occlusion method. Lungs were prepared for histopathology. In parallel groups, tumour necrosis factor (TNF)-alpha, neutrophils, and protein were evaluated in the BALF. L0.3 and L10 showed a time-dependent production of TNF-alpha preceding a massive neutrophil infiltration. In L10 BALF there was an increase in protein level at 24 and 48 h. Est and Edyn increased early in L0.3 (65%, 63%) and L10 (41%, 51%). In L10 deltaE, deltaP2, and deltaPtot showed a gradual rise. At 72 h all groups were similar. L0.3 showed an early increase in cellularity, which returned to normal at 72 h. L10 presented the same pattern with the cell count remaining elevated until 72 h. In conclusion, lipopolysaccharide inhalation led to elastic and viscoelastic pulmonary changes together with tumour necrosis factor-alpha production and neutrophil infiltration in mouse lung.