150 Skin damage induction by atmospheric particulate matter (PM0.3-2.5)

Characterization and in vitro biological effects of concentrated particulate matter from Mexico City

Exposure to environmental stressors like particulate matter (PM) and ultraviolet radiation (UV) induces cutaneous oxidative stress and inflammation and leads to skin barrier dysfunction and premature aging. Metals like iron or copper are abundant in PM and are known to contribute to reactive oxygen species (ROS) production. Although it has been suggested that topical antioxidants may be able to help in preventing and/or reducing outdoor skin damage, limited clinical evidence under real-life exposure conditions have been reported. The aim of the present study was to evaluate the ability of a topical serum containing 15% ascorbic acid, 0.5% ferulic acid, and 1% tocopherol (CF Mix) to prevent oxinflammatory skin damage and premature aging induced by PM + UV in a human clinical trial. A 4-day single-blinded, clinical study was conducted on the back of 15 females (18-40 years old). During the 4 consecutive days, the back test zones were treated daily with or without the CF Mix, followed by with/without 2 h of PM and 5 min of UV daily exposure. Application of the CF Mix prevented PM + UV-induced skin barrier perturbation (Involucrin and Loricrin), lipid peroxidation (4HNE), inflammatory markers (COX2, NLRP1, and AhR), and MMP9 activation. In addition, CF Mix was able to prevent Type I Collagen loss. This is the first human study confirming multipollutant cutaneous damage and suggesting the utility of a daily antioxidant topical application to prevent pollution induced skin damage.

Oxidative DNA damage and inflammatory responses in cultured human cells and in humans exposed to traffic-related particles

Worldwide epidemiological studies have shown that exposures to particulate matters (PMs), such as PM2.5 or PM10 , during pregnancy cause birth defects in the newborn. Although mechanistic understanding of such effects are not available, recent research using murine models highlights some key progress: (1) toxicity caused by PMs is a combined effects of particles and the adsorbed toxic pollutants, such as heavy metals, persistent organic pollutants, bacteria, and virus. Fine particles may hold on to pollutants and, therefore, reduce their toxicity or enhance the toxicity by carrying pollutants crossing the placental barrier; (2) smaller size, certain particle surface chemistry modifications, early developmental stage of placenta, and maternal diseases all aggravate PM-induced birth defects; (3) molecular events involved in such toxicity are begin to emerge: induction of oxidative stress, DNA damage, and alteration of molecular signaling or epigenetic events are some possible causes. Despite this progress, a clear understanding of PM-induced birth defects awaits further breakthroughs on many fronts, including epidemiological studies, animal models, nanotoxicity, and molecular mechanism investigations. Birth Defects Research (Part C) 108:196-206, 2016. © 2016 Wiley Periodicals, Inc.

Cutaneous aging is a complex biological process consisting of 2 elements: intrinsic aging, which is primarily determined by genetics, and extrinsic aging, which is largely caused by atmospheric factors, such as exposure to sunlight and air pollution, and lifestyle choices, such as diet and smoking. The role of the solar spectrum, comprised of ultraviolet light, specifically UVB (290-320nm) and UVA (320-400) in causing skin damage, including skin cancers, has been well documented. In recent years, the contribution of visible light (400-700nm) and infrared radiation (above 800nm) in causing skin damage, similar to the photodamage caused by UV light, is also being elucidated. In addition, other atmospheric factors such as air pollution (smog, ozone, particulate matter, etc.) have been implicated in premature skin aging. The skin damage caused by environmental exposure is largely attributable to a complex cascade of reactions inside the skin initiated by the generation of reactive oxygen species (ROS), which causes oxidative damage to cellular components such as proteins, lipids, and nucleic acids. These damaged skin cells initiate inflammatory responses leading to the eventual damage manifested in chronically exposed skin. Novel therapeutic strategies to combat ROS species generation are being developed to prevent the skin damage caused by atmospheric factors. In addition to protecting skin from solar radiation using sunscreens, other approaches using topically applied ingredients, particularly antioxidants that penetrate the skin and protect the skin from within, have also been well documented. This review summarizes current knowledge of atmospheric aggressors, including UVA, UVB, visible light, infrared radiation (IR), and ozone on skin damage, and proposes new avenues for future research in the prevention and treatment of premature skin aging caused by such atmospheric factors. New therapeutic modalities currently being developed are also discussed.

Human exposure to airborne particulate matter (PM), particularly its metal content, represents a growing public health concern due to its potential toxicological effects. While inhalation is generally considered the main exposure route, dermal absorption remains insufficiently explored. This study examined the in vitro percutaneous penetration of selected metals (As, Cd, Cr, Cu, Mn, Mo, Ni, Pb, V) from certified urban road dust (NIST SRM® 1649b) using human skin under both intact and abraded conditions. The particles were applied as a 1%w/v suspension in artificial sweat medium (pH4.5), and Franz diffusion cells were used to evaluate metal permeation over 24h. Complementary solubility tests in simulated sweat solution buffered topH 4.5 and 6.5 showed negligible pH dependence. Scanning electron microscopy revealed submicron primary particles (mean diameter 1.19±0.78μm) with a high tendency to form agglomerates, accounting for discrepancies with the hydrodynamic size reported in the SRM certificate. No detectable skin absorption was observed for Cd, Cr, and Cu, while the remaining metals showed enhanced permeation in damaged skin, confirming the role of barrier disruption in facilitating transdermal transport. Ni, Pb, and Mn exhibited the highest permeation levels, raising concern due to their sensitizing and toxic potential. These findings provide novel insights into the dermal bioavailability of PM-associated metals and highlight the importance of including skin exposure as a relevant pathway in environmental health risk assessments, especially for populations with compromised skin integrity or in high-exposure occupational settings.

Ambient particulate matter (PM) is a major contributor to environmental air pollution-associated skin damage. However, most published studies are observational or epidemiologic and have not mechanistically investigated the effects of air pollutants on cellular senescence and aging, particularly in combination with ultraviolet (UV) radiation. Herein, we analyzed whether UVA aggravates the PM-induced inflammatory cascade, which contributes to the aging of skin-derived cells. We hypothesized that cellular senescence is involved in PM&UVA-induced aging and tested whether an l-ascorbic acid compound (LAC), containing vitamin E and ferulic acid, can inhibit PM&UVA-induced aging. PM&UVA-exposed HDFs showed further elevated reactive oxygen species (ROS) levels detected by flow cytometry. We then demonstrated that PM induces MAPK signaling activation and the expression of AhR and NF-κB, responses that are both exacerbated by UVA. The levels of inflammatory cytokines, IL-1β and IL-6, were significantly higher in the PM&UVA-exposed group which resulted in increased transcription of MMPs, causing downregulation of type I collagen. Meanwhile, treatment with LAC reduced the levels of ROS and inflammatory cytokines. Additionally, PM&UVA-induced SA-β-gal production (staining assay) was reduced by LAC. These findings suggest a role of atmospheric pollution and UVA radiation in cellular senescence induction. Our findings also suggest a possible role of AhR inhibition by topical antioxidants to prevent atmospheric pollution-induced skin aging.

Particulate matter 2.5 (PM2.5), an atmospheric pollutant with an aerodynamic diameter of <2.5 μm, can cause serious human health problems, including skin damage. Since sebocytes are involved in the regulation of skin homeostasis, it is necessary to study the effects of PM2.5 on sebocytes. We examined the role of PM2.5 via the identification of differentially expressed genes, functional enrichment and canonical pathway analysis, upstream regulator analysis, and disease and biological function analysis through mRNA sequencing. Xenobiotic and lipid metabolism, inflammation, oxidative stress, and cell barrier damage-related pathways were enriched; additionally, PM2.5 altered steroid hormone biosynthesis and retinol metabolism-related pathways. Consequently, PM2.5 increased lipid synthesis, lipid peroxidation, inflammatory cytokine expression, and oxidative stress and altered the lipid composition and expression of factors that affect cell barriers. Furthermore, PM2.5 altered the activity of sterol regulatory element binding proteins, mitogen-activated protein kinases, transforming growth factor beta-SMAD, and forkhead box O3-mediated pathways. We also suggest that the alterations in retinol and estrogen metabolism by PM2.5 are related to the damage. These results were validated using the HairSkin® model. Thus, our results provide evidence of the harmful effects of PM2.5 on sebocytes as well as new targets for alleviating the skin damage it causes.

Airborne particulate matter (PM) extracts were investigated for their content of organic compounds and for the direct and oxidative DNA damage induced on lung epithelial cells A549. PM10 was seasonally collected at two monitoring sites (Stations 1 and 2), characterized by different traffic loads. The cells were exposed for 30 min to extracts of PM10 diluted at 0.025%, 0.05%, and 0.1% for summer samples, and at 0.05%, 0.1%, and 0.15% for winter samples. Oxidative and direct DNA damage were evaluated by formamidopyrimidine glycosylase (fpg) comet assay analyzing tail moment (TM) values from fpg-enzyme-treated cells (TMenz) and enzyme untreated cells (TM) respectively and by comet percentage analysis. Measurements relating to Station 2 showed higher levels of polycyclic aromatic hydrocarbons (PAHs), and their methyl-(methyl-PAHs) and nitro-(nitro-PAHs) derivatives in both the seasons. Nitro-PAH concentrations were higher in summer than in winter at both the stations. We found a significant increase of comet percentages at the highest dose of extract from both stations in summer and from Station 2 in winter. The TM and TMenz values relative to the summer sampling showed an early oxidative DNA damage induction also followed by direct DNA damage more evident at Station 2, that seems to correlate with the presence of higher nitro-PAH concentrations during the warm season. At both monitoring stations, the results from winter sampling campaign showed a direct DNA damage induction at 0.1% of extract and oxidative-direct DNA damage at the highest dose (0.15%).

Health risks associated with inhalation of fine particulate matter of 2.5 µm in diameter or smaller depend on their atmospheric levels and physicochemical properties. The relationships between chemical compositions and genotoxic activities of particles emitted by mineral industries, traffic and urban sources during summer and winter in the region of Provence-Alpes-Côte d'Azur (France) were investigated.The fine particles were separated in respect to water-soluble (13 minerals and metals) and organic-extractable (16 polycyclic aromatic hydrocarbons) components that were quantified. The chromosome damaging properties of the hydrophilic and lipophilic extracts were assessed using the centromeric micronucleus assay on a human lung fibroblast cell line.The composition of the fine particulate matter was variable and depended upon the sources and seasons. Both the hydrophilic and lipophilic extracts induced chromosome damage: (1) in hydrophilic extracts, Ca and Zn affected chromosome losses induction; (2) acenapthylene affected chromosome damage (breakages and losses) induction and naphthalene affected chromosome damage and losses induction in lipophilic extracts without metabolic activation; and (3) benzo[a]pyrene affected chromosome losses induction in lipophilic extracts with metabolic activation. Fine particulate matter arising from coal-fired power station, road traffic, and other urban sources were the most efficient to induce chromosome breakage.

Exposure to fine particulate matter smaller than 2.5 μm in diameter (PM2.5) has emerged as a critical environmental factor contributing to skin injury. As the skin is the body’s primary barrier against the external environment, it is directly susceptible to PM2.5, which induces oxidative stress, inflammation, premature aging, and disruption of skin barrier function. Increasing evidence demonstrates that PM2.5 damages both epidermal keratinocytes and dermal fibroblasts, leading to cellular dysfunction through alterations in major signaling pathways, including the aryl hydrocarbon receptor (AhR), nuclear factor kappa B (NF-κB), activator protein 1 (AP-1), mitogen-activated protein kinase (MAPK), and nuclear factor erythroid 2–related factor 2 (Nrf2). These molecular perturbations accelerate skin aging and impair protective functions, highlighting the need for effective intervention strategies. Botanicals and their bioactive phytochemicals have attracted growing interest for their antioxidant and anti-inflammatory properties, which may counteract PM2.5-induced damage. By targeting redox imbalance and inflammatory signaling, natural compounds represent a promising approach for protecting skin health. This review highlights the role of PM2.5 in skin injury and critically examines botanical strategies that may mitigate PM2.5-induced skin damage and premature aging.

Araliadiol, a triterpenoid compound isolated from Centella asiatica, exhibits diverse biological activities, including anti-cancer, neuroprotective, and hair growth-promoting properties. However, its protective effects against skin damage caused by environmental pollutants, such as urban particulate matter (UPM), remain unexplored. Given the critical role of oxidative stress in UPM-induced cellular damage, we investigated the potential of araliadiol as a dermoprotective agent and explored its underlying molecular mechanisms. The stability of araliadiol was evaluated at various temperature conditions and solvent conditions using high-performance liquid chromatography (HPLC). To explore the biological functions and signaling pathways affected by araliadiol, bioinformatic analyses including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Monarch phenotype analysis were performed. Cellular responses to araliadiol were assessed in HaCaT and HEK293T cells by measuring reactive oxygen species (ROS) levels and transcription of antioxidant genes. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and activator protein-1 (AP-1) signaling pathway was further examined using quantitative polymerase chain reaction (PCR), luciferase assay, western blotting, and immunofluorescence staining. The interaction between araliadiol and mitogen-activated protein kinase kinase 7 (MKK7) was investigated through molecular docking and cellular thermal shift assay (CETSA). DNA damage and apoptosis were examined using the comet assay, γ-H2AX staining, Annexin V/PI flow cytometry, and protein expression analysis. Araliadiol significantly reduced intracellular levels of ROS by upregulating key antioxidant genes, including HO-1, NQO1, TXNRD1, GCLC, and GCLM. Mechanistically, araliadiol promoted the expression and nuclear translocation of Nrf2, a master transcription factor involved in antioxidant defense. In parallel, araliadiol selectively activates the c-Jun N-terminal kinase (JNK)-AP-1 signaling cascade by directly binding to and activating MKK7, an upstream kinase involved in oxidative stress responses. Given the close association between oxidative stress, DNA damage, and apoptosis, we further investigated the protective capacity of araliadiol in this context. Araliadiol markedly attenuated UPM-induced DNA damage and apoptosis, as evidenced by reduced comet tail formation, decreased γ-H2AX levels, a lower proportion of Annexin V-positive cells, and modulation of apoptosis-related proteins. Meanwhile, although UPM exposure induced the expression of specific antioxidant-associated genes (TXNRD and GCLC), HO-1 protein expression, and AP-1 signaling, it failed to activate Nrf2 transcriptional activity. Instead, UPM exposure resulted in elevated intracellular ROS accumulation and increased DNA damage. Our findings suggest that UPM exposure alone elicited limited stress-adaptive antioxidant responses without effective cytoprotection. In contrast, araliadiol treatment independently activated robust antioxidant and cytoprotective signaling. Moreover, under UPM exposure, araliadiol further enhanced cellular defense through the activation of the Nrf2 and JNK-AP-1 signaling pathways. These results highlight the therapeutic potential of araliadiol as a dermoprotective agent derived from Centella asiatica, particularly in mitigating pollutant-induced skin damage.

Diesel particulate matter is one of the most dangerous environmental stressors affecting human health. Many plant-derived compounds with antioxidant and anti-inflammatory properties have been proposed to protect the skin from pollution damage. Curcumin (CUR) has a plethora of pharmacological activities, including anticancer, antimicrobial, anti-inflammatory and antioxidant. However, it has low bioavailability due to its difficult absorption and rapid metabolism and elimination. CUR encapsulation in nanotechnological systems and its combination with biopotentiators such as piperine (PIP) can improve its pharmacokinetics, stability and activity. In this study, ethosomes (ETs) were investigated for CUR and PIP delivery to protect the skin from damage induced by diesel particulate matter. ETs were produced by different strategies and characterized for their size distribution by photon correlation spectroscopy, for their morphology by transmission electron microscopy, and for their drug encapsulation efficiency by high-performance liquid chromatography. Franz cells enabled us to evaluate in vitro the drug diffusion from ETs. The results highlighted that ETs can promote the skin permeation of curcumin. The studies carried out on their antioxidant activity demonstrated an increase in the antioxidant power of CUR using a combination of CUR and PIP separately loaded in ETs, suggesting their possible application for the prevention of skin damage due to exogenous stressors. Ex vivo studies on human skin explants have shown the suitability of drug-loaded ETs to prevent the structural damage to the skin induced by diesel engine exhaust exposure.

Exposure to fine ambient particulate matter (PM2.5) is known to be associated with cardiovascular disease. To uncover the molecular mechanisms involved in cardiovascular toxicity of PM2.5, we investigated alterations in the protein profile of human umbilical vein endothelial cells (HUVECs) treated with PM2.5 using two-dimensional electrophoresis in conjunction with mass spectrometry (MS). A total of 31 protein spots were selected as differentially expressed proteins and identified by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) MS. The results demonstrated that DNA damage and cell apoptosis are important factors contributing to PM2.5-mediated toxicity in HUVECs. It is further proposed that PM2.5 can inhibit superoxide dismutase (SOD) activity and increase reactive oxygen species (ROS) and malonaldehyde (MDA) production in a concentration-dependent manner. Induction of apoptosis and DNA damage through oxidative stress pathways may be one of the key toxicological events occurring in HUVECs under PM2.5 stress. These results indicated that the toxic mechanisms of PM2.5 on cardiovascular disease are related to endothelial dysfunction.

Urban particulate matter (UPM) includes particles of size smaller than 10 microm (PM10), which may impact on human respiratory and cardiovascular health. It has been reported previously that PM10 can induce DNA damage. We have collected size-fractionated PM10 at the roadside and measured the induction of DNA damage by different-sized UPM using the alkaline Comet assay and the plasmid strand-break assay. We found that foil disks were more suitable for collecting UPM than quartz fiber filters, as the UPM could be easily extracted from the foil disks and accurately weighed. Using the Comet assay, all size fractions induced DNA damage in A549 lung epithelial cells, with the finer fractions (D50% = 0.65 microm and lower) inducing the most damage. In the plasmid strand-break assay, in which DNA damage is induced by free-radical species generated in solution, the most damage was also induced by the finer fractions, although the finest fraction (D50% < 0.43 microm) did not induce as much damage as D50% = 0.65 and 0.43 microm. When an organic extract of a standard UPM sample was compared to the whole particles and the washed particles in the Comet assay, it was found that around 75% of the damage induced by the whole UPM could be induced by the organic extract. These results show that finer particulates have the greatest ability to induce DNA damage in lung epithelial cells and naked DNA, and that both organic and inorganic components of the UPM contribute to its genotoxic effects.