Interactions between inhalable aged microplastics and lung surfactant: Potential pulmonary health risks.

The relationship between microplastics (MPs) and human respiratory health has garnered significant attention since inhalation constitutes the primary pathway for atmospheric MP exposure. While recent studies have revealed respiratory risks associated with MPs, virgin MPs used as plastic surrogates in these experiments did not represent the MPs that occur naturally and that undergo aging effects. Thus, the effects of aged MPs on respiratory health remain unknown. We herein analyzed the interaction between inhalable aged MPs with lung surfactant (LS) extracted from porcine lungs vis-à-vis interfacial chemistry employing in-vitro experiments, and explored oxidative damage induced by aged MPs in simulated lung fluid (SLF) and the underlying mechanisms of action. Our results showed that aged MPs significantly increased the surface tension of the LS, accompanied by a diminution in its foaming ability. The stronger adsorptive capacity of the aged MPs toward the phospholipids of LS appeared to produce increased surface tension, while the change in foaming ability might have resulted from a variation in the protein secondary structure and the adsorption of proteins onto MPs. The adsorption of phospholipid and protein components then led to the aggregation of MPs in SLF, where the aged MPs exhibited smaller hydrodynamic diameters in comparison with the unaged MPs, likely interacting with biomolecules in bodily fluids to exacerbate health hazards. Persistent free radicals were also formed on aged MPs, inducing the formation of reactive oxygen species such as superoxide radicals (O2•-), hydrogen peroxide (HOOH), and hydroxyl radicals (•OH); this would lead to LS lipid peroxidation and protein damage and increase the risk of respiratory disease. Our investigation was the first-ever to reveal a potential toxic effect of aged MPs and their actions on the human respiratory system, of great significance in understanding the risk of inhaled MPs on lung health.

Interactions between CuO NPs and PS: The release of copper ions and oxidative damage.

Copper oxide nanoparticles (CuO NPs) can adversely affect lung health possibly by inducing oxidative damage through the release of copper ions. However, the migration and transformation processes of CuO NPs in lung lining fluid is still unclear, and there are still conflicting reports of redox reactions involving copper ions. To address this, we examined the release of copper ions from CuO NPs in simulated lung fluid supplemented with pulmonary surfactant (PS), and further analyzed the mechanisms of PS-CuO NPs interactions and the health hazards. The results showed that the phospholipid of PS was adsorbed on the particle surface, which not only induced aggregation of the particles but also provided a reaction environment for the interaction of PS with CuO NPs. PS was able to promote the release of ions from CuO NPs, of which the protein was a key component. Lipid peroxidation, protein destabilization, and disruption of the interfacial chemistry also occurred in the PS-CuO NPs interactions, during which copper ions were present only as divalent cations. Meanwhile, the contribution of the particle surface cannot be neglected in the oxidative damage to the lung caused by CuO NPs. Through reacting with biomolecules, CuO NPs accomplished ion release and induced oxidative damage associated with PS. This research was the first to reveal the mechanism of CuO NPs releasing copper ions and inducing lipid oxidative damage in the presence of PS, which provides a new idea of transition metal-induced health risk in human body.

Potential hazards associated with interactions between diesel exhaust particulate matter and pulmonary surfactant.

Long term exposure to diesel exhaust particulate matter (DEPM) can induce numerous adverse health effects to the respiratory system. Understanding the interaction between DEPM and pulmonary surfactant (PS) can be an essential step toward preliminary evaluation of the impact of DEPM on pulmonary health. Herein, DEPM was explored for its interaction with 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC), the major component of PS. The results indicated that the surface pressure-area (π-A) isotherms of DPPC monolayers shifted toward lower molecular areas and the compression modulus (CS-1) reduced in the presence of DEPM. Atomic force microscopy image showed that DEPM can disrupt the ultrastructure of DPPC monolayers along with the direction of lateral compression. In addition, DPPC can in turn condition the surface properties of DEPM, permitting its agglomeration in aqueous media, which was attributed to the adsorption of DEPM to DPPC. Furthermore, the particle-bound polycyclic aromatic hydrocarbons (PAHs) could be desorbed from DEPM by the solubilization of DPPC and it was positively correlated with the hydrophobicity of PAHs. These findings revealed the toxicity of DEPM-associated PAHs and the role of DPPC in facilitating the removal of the inhaled particles, which can provide a new insight into the potential hazards of airborne particles on lung health.

Potential health risks of the interaction of microplastics and lung surfactant.

Microplastics (MPs), as pollutants of environmental concern, are correlated with increased risk of various respiratory diseases. Nevertheless, whether or not MPs have adverse influences on the interfacial properties of lung surfactant (LS), and its effect on the generation of reactive oxygen species are poorly understood. In the present study, natural LS extracted from porcine lungs was used to investigate the interaction with polystyrene as a representative MPs. The results showed that the phase behavior, surface tension, and membrane structure of the LS were altered in the presence of polystyrene. Adsorption experiments demonstrated that in the mixed system of polystyrene and LS (the main active ingredients are phospholipids and proteins), adsorption of phospholipid components by polystyrene was notably higher than that of proteins. Moreover, polystyrene can accelerate the conversion between ascorbic acid and deoxyascorbic acid, thereby producing hydrogen peroxide (HOOH) in simulated lung fluid (containing LS) and further giving rise to an increase in the content of hydroxyl radicals (•OH). This work provides new insight into the potential hazard of MPs in human respiratory system, which is helpful for deeply understanding the unfavorable physicochemical effects of MPs exposure and the role of inhaled MPs on lung health.

Evaluation of the permeability and potential toxicity of polycyclic aromatic hydrocarbons to pulmonary surfactant membrane by the parallel artificial membrane permeability assay model.

Polycyclic aromatic hydrocarbons (PAHs) can penetrate and accumulate in the pulmonary surfactant (PS) membranes, leading to abnormalities of biological macromolecules and the destruction of membrane structure and properties. In the present study, the bioavailability, apparent permeability, effective permeability and residual coefficient of 10 PAHs on PS membrane was assessed by the parallel artificial membrane permeability assay (PAMPA). The influence of various forces on permeability is obtained by analyzing the correlation between parameters and physicochemical properties. Research shows that octanol-water partition coefficient (Kow) cannot directly predict permeability, and permeability has no significant relationship with polarity. Dispersion, induction, coupling/polarization promote permeation, while hydrogen bonded acid and n-n electron pair inhibit permeation. Further surface pressure-area (π-A) isotherms test and Brewster angle microscope observation manifested that there are huge differences in the transmembrane ability and effects on the membrane of PAHs with different structures. This work has considerable significance that will help to evaluate the bioavailability and human health risk of PAHs.

A Deeper Insight into the Interfacial Behavior and Structural Properties of Mixed DPPC/POPC Monolayers: Implications for Respiratory Health.

1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-oleyl-sn-glycerol-3-phosphorcholine (POPC) are important components in pulmonary surfactants (PSs), of which the relative content is related to lung compliance. Herein, the phase behavior and thermodynamic structure of mixed DPPC/POPC monolayers were studied to elucidate the intermolecular interaction between DPPC and POPC molecules. Surface pressure-molecular area isotherms demonstrated that POPC significantly affected the phase behavior of the lipid domain structure as a function of its concentration. The compression modulus of the mixed monolayers reduced with the increase in POPC proportion, which can be attributed to the intermolecular repulsion between DPPC and POPC. Brewster angle microscopy analysis showed that the ordered structure of the monolayers trended toward fluidization in the presence of POPC. Raman spectroscopy results revealed that the change in C-C skeleton stretching vibration was the main cause of the decrease in the monolayer packing density. These findings provide new insights into the role of different phospholipid components in the function of PS film at a molecular level, which can help us to understand the synergy effects of the proportional relationship between DPPC and POPC on the formation and progression of lung disease and provide some references for the synthesis of lung surfactants.

Interfacial interaction between benzo[a]pyrene and pulmonary surfactant: Adverse effects on lung health.

Inhaled polycyclic aromatic hydrocarbons (PAHs) can directly interact with the lung surfactant (PS) lining of alveoli, thereby affecting the normal physiological functions of PS, which is a serious threat to lung health. In spite of the extensive study of benzo[a]pyrene (BaP, a representative of PAHs), its potential biophysical influence on the natural PS is still largely unknown. In this study, the interfacial interaction between PS (extracted from porcine lungs) and BaP is investigated in vitro. The results showed that the surface tension, phase behavior, and interfacial structure of the PS monolayers were obviously altered in the presence of BaP. A solubilization test manifested that PS and its major components (dipalmitoyl phosphatidylcholine, DPPC; bovine serum albumin, BSA) could in turn accelerate the dissolution of BaP, which followed the order: PS > DPPC > BSA, and mixed phospholipids were significantly responsible for the solubilization of BaP by PS. In addition, solubilization of BaP also enhanced the consumption of hydroxyl radicals (·OH) in the simulated lung fluid, which could disturb the balance between oxidation and antioxidation.

Interaction of pulmonary surfactant with silica and polycyclic aromatic hydrocarbons: Implications for respiratory health.

Understanding the interaction between pulmonary surfactant (PS) and inhalable pollutants is vital for risk assessment of respiratory health. Here, PS extracted from porcine lung (EPS) was used to investigate the interaction of PS with nano-silica particles and polycyclic aromatic hydrocarbons (PAHs). Our results demonstrated that silica significantly affected the phase behavior and foaming ability of EPS; EPS and its major components (dipalmitoyl phosphatidylcholine, DPPC; bovine serum albumin, BSA) exhibited great enhancing effect on PAHs solubility, which follows the order: EPS > DPPC > BSA, and it was positively correlated with the hydrophobicity of PAHs. Further experiments demonstrated that mixed phospholipids of EPS were largely responsible for the solubilization of EPS on PAHs. In the presence of EPS, DPPC or BSA, adsorption of PAHs by silica was notably inhibited, indicating competitive adsorption between PAHs and PS components on silica. These findings provide evidence for the surface chemistry by which PS facilitates the solubilization of PAHs and reducing the adsorption of PAHs on silica, which may be helpful for deeply understanding the effects of particulate matter and PAHs on lung health.

Serum microRNA miR-206 is decreased in hyperthyroidism and mediates thyroid hormone regulation of lipid metabolism in HepG2 human hepatoblastoma cells.

The actions of thyroid hormone (TH) on lipid metabolism in the liver are associated with a number of genes involved in lipogenesis and lipid metabolism; however, the underlying mechanisms through which TH impacts on lipid metabolism remain to be elucidated. The present study aimed to investigate the effects of hyperthyroidism on the serum levels of the microRNA (miR) miR­206 and the role of miR­206 on TH­regulated lipid metabolism in liver cells. Serum was obtained from 12 patients diagnosed with hyperthyroidism and 10 healthy control subjects. Human hepatoblastoma (HepG2) cells were used to study the effects of triiodothyronine (T3) and miR­206 on lipid metabolism. Expression of miR­206 in serum and cells was determined by reverse transcription­quantitative polymerase chain reaction analysis. Lipid accumulation in HepG2 cells was assessed with Oil Red O staining. Suppression or overexpression of miR­206 was performed via transfection with a miR­206 mimic or miR­206 inhibitor. Serum miR­206 was significantly decreased in patients with hyperthyroidism compared with euthyroid controls. Treatment of HepG2 cells with T3 led to reduced total cholesterol (TC) and triglyceride (TG) content, accompanied by reduced miR­206 expression. Inhibition of endogenous miR­206 expression decreased intracellular TG and TC content in HepG2 cells. By contrast, overexpression of miR­206 in HepG2 partially prevented the reduction in TG content induced by treatment with T3. In conclusion, serum miR­206 expression is reduced in patients with hyperthyroidism. In addition, miR­206 is involved in T3­mediated regulation of lipid metabolism in HepG2 cells, indicating a role for miR­206 in thyroid hormone­induced disorders of lipid metabolism in the liver.