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Fine particulate matter (PM2.5) increases the risks of lung cancer. Epigenetics provides a new toxicology mechanism for the adverse health effects of PM2.5. However, the regulating mechanisms of PM2.5 exposure on candidate gene DNA methylation changes in the development of lung cancer remain unclear. Abnormal expression of the glutathione S transferase (GST) gene is associated with cancer. However, the relationship between PM2.5 and DNA methylation-mediated GST gene expression is not well understood. In this study, we performed GST DNA methylation analysis and GST-related gene expression in human A549 cells exposed to PM2.5 (0, 50, 100 µg/mL, from Taiyuan, China) for 24 h (n = 4). We found that PM2.5 may cause DNA oxidative damage to cells and the elevation of GSTP1 promotes cell resistance to reactive oxygen species (ROS). The Kelch-1ike ECH-associated protein l (Keap1)/nuclear factor NF-E2-related factor 2 (Nrf2) pathway activates the GSTP1. The decrease in the DNA methylation level of the GSTP1 gene enhances GSTP1 expression. GST DNA methylation is associated with reduced levels of 5-methylcytosine (5mC), DNA methyltransferase 1 (DNMT1), and histone deacetylases 3 (HDAC3). The GSTM1 was not sensitive to PM2.5 stimulation. Our findings suggest that PM2.5 activates GSTP1 to defend PM2.5-induced ROS and 8-hydroxy-deoxyguanosine (8-OHdG) formation through the Keap1/Nrf2 signaling pathway and GSTP1 DNA methylation. [ABSTRACT FROM AUTHOR]

1-Nitropyrene (1-NP) is a mutagenic and carcinogenic pollutant very widespread in the environment. However, the relative investigations on genotoxicity, oxidative stress and metabolic enzymes in lungs of mammalian caused by 1-NP have not been fully established. In this study, the 1-NP solutions at 3 dosages (1.0 × 10 −5 , 4.0 × 10 −5 and 1.6 × 10 −4 mg/kg body weight) were respectively given to rats by the intratracheal instillation. The responses of 1-NP on DNA damage and repair, oxidative stress and metabolism biomarkers in rat lungs after exposure to 1-NP were measured. The results showed 1-NP at three dosages induced obvious DNA strand breaks, 8-OH-dG formation and DNA-protein cross-link in rat lungs compared with the control. Higher dosage 1-NP (4.0 × 10 −5 and 1.6 × 10 −4 mg/kg body weight) greatly activated DNA repair gene OGG1 and inhibited MTH1 and XRCC1 expressions, and they significantly elevated the levels of GADD153, heme oxygenase-1 and malondialdehyde and decreased SOD activity, accompanied by the increases of CYP450, CYP1A1, CYP1A2 and GST levels. These results suggested the genotoxicity of 1-NP might rely on 1-NP-caused DNA damage and its combined effects on the suppression of DNA repair and the enhancement of oxidative stress and metabolic enzyme activity. [ABSTRACT FROM AUTHOR]

Epidemiological studies suggested that ambient fine particulate matter (PM 2.5 ) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM 2.5 -induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM 2.5 with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM 2.5 exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM 2.5 exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na + K + -ATPase and Ca 2+ -ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM 2.5 -induced heart injury, and may have relations with cardiovascular disease. [ABSTRACT FROM AUTHOR]

The atmosphere's fine particulate matter (PM2.5) can enter the liver through the circulatory system, leading to hepatic inflammation and fibrosis. As a non-flavonoid polyphenolic compound, resveratrol (RES) has anti-oxidant, anti-inflammatory and hepatoprotective effects, but the molecular mechanisms of liver fibrosis induced by PM2.5 exposure are still limited. In this study, we established an in vitro cell model to investigate the intervention effect of RES with different concentrations (5 and 20 μmol/mL) on mouse hepatic stellate cells (mHSCs) injury induced by PM2.5 (100 μg/mL). We determined the cell viability in mHSCs after treatment with PM2.5 or/and RES for 24 h. We investigated the intracellular oxidative stress by detecting the changes in reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) levels. We also measured the protein expressions of fibrosis-related genes (α-SMA, Collagen I and Collagen III) and key genes (SIRT1, NF-κB, NLRP3, Cleaved-Caspase1, IL-1β) in the NLRP3 pathway in mHSCs exposed to PM2.5 with or without RES. The results showed that (1) PM2.5 has cytotoxic effects on mHSCs, whereas RES (5 μmol/L and 20 μmol/L) inhibited PM2.5-induced cytotoxicity and LDH leakage; (2) RES effectively reduces ROS and MDA production caused by PM2.5 while concurrently enhancing SOD levels, thereby improving cellular anti-oxidant capacity; (3) the expression of α-SMA, Collagen I and Collagen III were notably downregulated in the PM2.5 plus RES treatment group compared to the PM2.5-exposed group; (4) RES significantly increased SIRT1 expression and decreased the expression of NF-κB, NLRP3, Cleaved-Caspase1 and IL-1β in mHSCs exposure to PM2.5 compared to the PM2.5 group. These results demonstrate that RES can up-regulate SIRT1 and mitigate PM2.5-induced fibrosis by suppressing oxidative stress in mHSCs and the SIRT1/NF–κB/NLRP3 pathway activated by PM2.5. [ABSTRACT FROM AUTHOR]

Exposure to fine particulate matter (PM 2.5 ) has a close association with respiratory damage. Vitamin c and quercetin have been documented to possess antioxidant and anti-inflammation properties. However, their potential protective effects against PM 2.5 -induced respiratory damage have not been evaluated yet. Hence, the study was aimed to investigate their protective effects and delineate the possible mechanisms. The results indicated that PM 2.5 depleted the cell viability of 16HBE cells, elevated reactive oxygen species (ROS) generation, and inhibited mitochondrial genes expressions, including fusion proteins Mfn1 and OPA1 , along with biogenesis markers SIRT1 and p53R2 . Additionally, the damage of mitochondrial morphology was observed upon PM 2.5 exposure using both JC-1 and MitoTracker Red staining. Expressions of mitochondrial respiratory chain genes including NDUFS2 and UQCRI1 were also attenuated by PM 2.5 exposure. Furthermore, PM 2.5 promoted the mRNA levels of NADPH oxidase and inflammation cytokines. However, the addition of vitamin c or quercetin strikingly antagonized the PM 2.5 -induced toxic effects. Collectively, these findings suggest that vitamin c and quercetin have repressive roles in respiratory oxidative damage incurred by PM 2.5 , which provide the theoretical basis about intervention and control of food nutrients on PM 2.5 -induced human adverse health. [ABSTRACT FROM AUTHOR]

The aim of the study is to investigate chemical compositions of fine chalk dust particles (chalk PM 2.5 ) and examine their adverse effects on alveolar macrophages (AMs) in vitro . Morphologies and element concentrations of individual chalk particles were analyzed by using the quantitative energy-dispersive electron probe X-ray microanalysis (ED-EPMA). The oxidative response of AMs and the potential to generate nitric oxide (NO) by luminol-dependent chemiluminescence (CL) and nitrate reductase method were assessed 4 h following the treatment of AMs with differing dosages of fine chalk particles, respectively. Oxidative stress and cytotoxicity elicited by chalk PM 2.5 were also examined. The results showed that fine chalk particles were mainly composed of gypsum, calcite, dolomite and a little amount of organic adhesives. Exposure to chalk PM 2.5 at 100 μg mL −1 or 300 μg mL −1 significantly increased intracellular catalase, malondialdehyde, and NO levels and decreased superoxide dismutase level in AMs, leading to leakage of lactate dehydrogenase (LDH) and reduction of the cell viability. Furthermore, luminol-dependent CL from respiratory burst in AMs was enhanced. It was suggested that chalk PM 2.5 could make oxidative damages on AMs and result in cytotoxicity, being likely attributed to excessive reactive oxygen species or reactive nitrogen species induced by mixture of fine gypsum and calcite/dolomite particles. [ABSTRACT FROM AUTHOR]

Background: The toxicological effects of fine particulate matter (PM2.5) on the cardiopulmonary and nervous systems have been studied widely, whereas the study of PM2.5 on systemic toxicity is not in-depth enough. Lipopolysaccharide (LPS) can cause multiple organ damage. The combined effects of co-exposure of PM2.5 plus LPS on the stomach, spleen, intestine, and kidney are still unclear. Purpose: This study was aimed to explore the toxicological effects of co-exposure of PM2.5 and LPS on the different organs of mice. Research Design and Study Sample Using a real-ambient PM2.5 exposure system and an intraperitoneal LPS injection mouse model, we investigated multiple organ damage effects on male BALB/c mice after co-exposure of PM2.5 plus LPS for 23 weeks in Linfen, a city with a high PM2.5 concentration in China. Data Collection: Eosin-hematoxylin staining, ELISA and the biochemical assay analysed the toxicological effects. Results: The pathological tissue injury on the four organs above appeared in mice co-exposed to PM2.5 plus LPS, accompanied by the body weight and stomach organ coefficient abnormality, and significant elevation of pro-inflammatory cytokines levels, oxidative stress in the spleen and kidney, and levels of kidney injury molecule (KIM-1) increase in the kidney. There were tissue differences in the pathological damage and toxicological effects on mice after co-exposure, in which the spleen and kidney were more sensitive to pollutants. In the PM2.5 + LPS group, the superoxide dismutase inhibition and catalase (CAT) activity promotion in the kidney or spleen of mice were significant relative to the PM2.5 group; the CAT and interleukin-6 (IL-6) levels in the spleen were raised considerably compared with the LPS group. Conclusions: These findings suggested the severity and sensitivity of multiple organ injuries in mice in response to PM2.5 plus LPS. [ABSTRACT FROM AUTHOR]

Abstract The risk of development of asthma, a multi-faceted chronic disease, increases as a result of exposure to PM 2.5. However, the mechanism underlying asthma-related metabolic changes caused by PM 2.5 exposure is unclear. Here, we investigated the major metabolic changes, metabolic pathways involved, and underlying molecular mechanisms in mice with PM 2.5 exposure-induced asthma. Forty-eight adult female mice were randomly assigned to control (C), low concentration-PM 2.5 exposure: 0.50 mg kg−1 (L), medium concentration-PM 2.5 exposure: 1.58 mg kg−1 (M), and high concentration-PM 2.5 exposure: 4.98 mg kg−1 (H) groups. M and H groups presented significantly higher IL-4, IL-8, IL-1β, IL-5, IL-13, and OVA-specific IgE levels, and significantly lower IFN-γ levels, than the C group, as well as significantly increased eosinophil count and MUC5AC expression in the lung tissue. These findings indicate that exposure to medium and high concentrations of PM 2.5 induced asthma in mice. Statistical analyses identified 13 asthma-related major metabolites, which were analyzed by gas chromatography-mass spectrometry (GC-MS). Meta Mapp Software revealed 4 major metabolic pathways. PM 2.5 -induced ATP requirement and oxidative stress may perturb metabolic processes in asthma. The present findings increase our understanding of the toxic effect of PM 2.5 in the development of asthma and identify potentially useful biomarkers. Graphical abstract Image 1 Highlights • PM 2.5 induces asthma in mice. • GC-MS analysis identified 13 biomarkers in PM 2.5 -induced asthmatic mice. • Screening identified four metabolic pathways involved in the pathogenesis of asthma. • PM 2.5 regulates amino acid and purine metabolism by disrupting the TCA cycle. [ABSTRACT FROM AUTHOR]

Abstract Exposure to ambient fine particulate matter (PM 2.5) is associated with neurodegenerative diseases. Mitochondrion is key to brain degeneration. However, the underlying mechanism of PM 2.5 -induced brain injury, especially mitochondrial damage, is still unclear. In this study, changes in mitochondrial dynamics, mitochondrial permeability transition pore (mPTP), mitochondrial DNA (mtDNA) and oxidative stress in human SH-SY5Y cells exposed to PM 2.5 at different concentrations (0, 25, 100, and 250 μg mL−1) were investigated. The results showed that PM 2.5 caused more mitochondrial swell, accompanied by the opening of mPTP and the decrease of ATP levels, mitochondrial membrane potential and mtDNA copy number in SH-SY5Y cells. PM 2.5 significantly enhanced the expression of mitochondrial fission/fusion genes (Drp1 and OPA1) and affected the gene expression of CypD, SIRT3, and COX Ⅳ in SH-SY5Y cells. Besides, PM 2.5 triggered the increase of cellular ROS, Ca2+ and Aβ-42 levels, inhibition of manganese-superoxide dismutase (SOD 2) activities, reduction of GSH levels GSH/GSSG ratio, and elevation of mitochondrial malondialdehyde contents. It suggests that mitochondrial dysfunction and oxidative stress are the potential mechanisms underlying PM 2.5 -induced brain nerve cell injury, which may be related to neurological diseases. Additionally, our study elucidated that PM 2.5 components trigger different cytotoxicity. Graphical abstract Image 1 Highlights • PM 2.5 induces mitochondrial morphological damage of SH-SY5Y cells. • PM 2.5 triggers mitochondrion permeability transition pore opening. • PM 2.5 reduces ATP, mitochondrial membrane potential and mtDNA copy number. • PM 2.5 -caused oxidative stress related to enhancement of ROS, SIRT3 and Aβ-42 levels. [ABSTRACT FROM AUTHOR]