Layers of pulmonary lipids on an aqueous substrate at non-equilibrium conditions can decrease the surface tension of water to quite low values. This is connected with different relaxation processes occurring at the interface and the associated changes in the surface layer structure. Results of measurements by the combination of methods like surface rheology, ellipsometry, Brewster angle microscopy, and IRRAS for spread layers of lipid mixtures open a possibility to specify the dynamics of structural changes at conditions close to the physiological state. At sufficiently low surface tension values (below 5 mN/m) significant changes in the ellipsometric signal were observed for pure DPPC layers, which can be related to a transition from 2D to 3D structures caused by the layer folding. The addition of other lipids can accelerate the relaxation processes connected with squeezing-out of molecules or multilayer stacks formation hampering thereby a decrease of surface tension down to low values corresponding to the folding of the monolayer.

Exposure to ozone causes decrements in pulmonary function, a response associated with alterations in lung lipids. Pulmonary lipid homeostasis is dependent on the activity of peroxisome proliferator activated receptor gamma (PPARγ), a nuclear receptor that regulates lipid uptake and catabolism by alveolar macrophages (AMs). Herein, we assessed the role of PPARγ in ozone-induced dyslipidemia and aberrant lung function in mice. Exposure of mice to ozone (0.8 ppm, 3 h) resulted in a significant reduction in lung hysteresivity at 72 h post exposure; this correlated with increases in levels of total phospholipids, specifically cholesteryl esters, ceramides, phosphatidylcholines, phosphorylethanolamines, sphingomyelins, and di- and triacylglycerols in lung lining fluid. This was accompanied by a reduction in relative surfactant protein-B (SP-B) content, consistent with surfactant dysfunction. Administration of the PPARγ agonist, rosiglitazone (5 mg/kg/day, i.p.) reduced total lung lipids, increased relative amounts of SP-B, and normalized pulmonary function in ozone-exposed mice. This was associated with increases in lung macrophage expression of CD36, a scavenger receptor important in lipid uptake and a transcriptional target of PPARγ. These findings highlight the role of alveolar lipids as regulators of surfactant activity and pulmonary function following ozone exposure and suggest that targeting lipid uptake by lung macrophages may be an efficacious approach for treating altered respiratory mechanics.

This study investigated the potential protective role of aqueous leafextracts of Chromolaena odorata and Tridax procumbens against pulmonary toxicity induced by doxorubicin. To this end, the effects of these extracts on the profiles of pulmonary biomarkers, lipids and electrolytes were monitored in doxorubicin-treated rats. Doxorubicin was intraperitoneally administered at 15 mg/kg body weight (48 h prior to sacrifice); metformin was orally administered daily at 250 mg/kg body weight (for 14 days); and both extracts were orally administered daily at 50, 75 and 100 mg/kg body weight (for 14 days).The concentrations of pulmonary malondialdehyde, cholesterol, triglyceride, calcium, chloride and sodium of Test control were significantly higher (P < 0.05) than those of the other groups. However, the concentrations of pulmonary ascorbic acid, reduced glutathione, magnesium and potassium as well as pulmonary catalase, glutathione peroxidase and superoxide dismutase activities of Test control were significantly lower (P < 0.05) than those of the other groups.The administration of the extracts prevented doxorubicin-induced adverse alterations in the profiles of pulmonary biomarkers of oxidative stress, cholesterol and electrolytes and maintained them within the normal ranges .Therefore, these herbal preparations from C. odorata and T. procumbens are promising candidates for the prevention/alleviation of doxorubicin-induced pulmonary toxicity.

Background: Asthma is a respiratory disease with chronic airway inflammatory, and individuals with asthma exacerbations is one of the most frequent causes of hospitalization. Huanglong antitussive granule (HL Granule), a Chinese proprietary herbal medicine, has been proved to be effective in the clinical treatment of pulmonary disease. This study is devoted to the pharmacodynamics of HL Granule in acute asthma and the possible mechanism from the perspective of lipidomics. Methods: Mice were divided into four groups, control group, acute asthma model group, HL Granule treatment and montelukast sodium treatment group. Acute asthma was induced by ovalbumin (OVA). Histopathology, pulmonary function and enzyme linked immunosorbent assay (ELISA) were used to validated model and effect of HL Granule. Lipids were detected by ultra-high-performance liquid chromatography coupled to hybrid Quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) and identified by MS-DAIL and built-in Lipidblast database. Differentially expressed lipids recalled in HL Granule treatment group were extracted for heatmap, enrichment analysis and correlation analysis. Results: HL Granule was effective in decreasing airway hyperresponsiveness (AHR), airway inflammatory and the levels of IL-4 and IL-5. A total of 304 and 167 lipids were identified in positive and negative ion mode, respectively. Among these, 104 and 73 lipids were reserved in HL Granule group (FDR < 0.05), including acylcarnitine (ACar), fatty acid (FA), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), lysophosphatidylethanolamine (LPE), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidylserine (PS), diglyceride (DG), triglyceride (TG), sphingomyelin (SM) and ceramide (Cer). Furthermore, 118 and 273 correlations among 47 and 96 lipids in the positive and negative were observed, with ether-linked phosphatidylethanolamine (PEe) and phosphatidylcholine (PCe) (FDR < 0.001, Spearman correlation coefficient r 2 > 0.75). Conclusion: HL Granule might improve pulmonary lipid homeostasis and could be used as an alternative or supplementary therapy in clinical for the treatment of asthma.

Inflammatory macrophages are known to contribute to ozone toxicity. Farnesoid X receptor (FXR) is a nuclear receptor involved in regulating bile acid and lipid homeostasis; it also exerts anti-inflammatory activity by suppressing macrophage NF-κB. Herein, we analyzed the role of FXR in regulating macrophage activation in the lung following ozone exposure. Treatment of wild-type (WT) mice with ozone (0.8 ppm, 3 h) resulted in increases in proinflammatory (F4/80+CD11c+CD11b+Ly6CHi) and anti-inflammatory (F4/80+CD11c+CD11b+Ly6CLo) macrophages in the lung. The accumulation of proinflammatory macrophages was increased in FXR-/- mice compared with WT mice; however, anti-inflammatory macrophage activation was blunted as reflected by reduced arginase and mannose receptor expression, a response correlated with decreased Nur77. This was associated with prolonged oxidative stress, as measured by 4-hydroxynonenal-modified proteins in the lung. Loss of FXR was accompanied by protracted increases in lung NF-κB activity and its target, inducible nitric oxide synthase in response to ozone. Levels of Tnf-α, Il-1β, Ccr2, Ccl2, Cx3cr1, and Cx3cl1 were also increased in lungs of FXR-/- relative to WT mice; conversely, genes regulating lipid homeostasis including Lxrα, Apoe, Vldlr, Abcg1, and Abca1 were downregulated, irrespective of ozone exposure. In FXR-/- mice, ozone caused an increase in total lung phospholipids, with no effect on SP-B or SP-D. Dyslipidemia was correlated with blunting of ozone-induced increases in positive end-expiratory pressure-dependent quasi-static pressure volume curves indicating a stiffer lung in FXR-/- mice. These findings identify FXR as a regulator of macrophage activation following ozone exposure suggesting that FXR ligands may be useful in mitigating inflammation and oxidative stress induced by pulmonary irritants.