Iron-doped diesel exhaust early-in-life inhalation-induced cardiopulmonary toxicity in chicken embryo: Roles of ferroptosis and acyl hydrocarbon signaling.

Diesel exhaust (DE) is a major contributor to air pollution. Iron-doping could improve diesel burning efficacy and decrease emission, however, it will also change the composition of DE, potentially enhancing the toxicities. This study is aimed to assess iron-doped DE-induced cardiopulmonary toxicity in an established in ovo early-in-life inhalation exposure chicken embryo model, and to explore potential mechanisms. Ferrocene (205, 410, 820,1640 mg/L, equivalent to 75, 150, 300, 600 ppm iron mass) was added to diesel fuel, DE was collected from a diesel generator, and then exposed to embryonic day 18-19 chicken embryo via in ovo inhalation. Hatched chickens were kept for 0, 1, or 3 months, and then sacrificed. Histopathology, electrocardiography along with biochemical methods were used to assess cardiopulmonary toxicities. For mechanistic investigation, inhibitor for ferroptosis (ferrostatin-1) or Acyl hydrocarbon receptor (PDM2) were administered before DE (with or without iron-doping), and the cardiopulmonary toxicities were compared. Characterization of DE particles indicated that addition of ferrocene significantly elevated iron content. Additionally, the contents of major toxic polycyclic aromatic hydrocarbons decreased following addition of 820 mg/L ferrocene, but increased at other doses. Remarkable cardiopulmonary toxicities, in the manifestation of elevated heart rates, cardiac remodeling and cardiac/pulmonary fibrosis were observed in animals exposed to iron-doped DEs, in which the addition of ferrocene significantly enhanced the toxicities. Both ferrostatin-1 and PDM2 pretreatment could effectively alleviate the observed effects in animals exposed to iron-doped DE. Inhibition of AhR signaling seems to be capable of alleviating changes to ferroptosis related molecules following exposure to iron-doped DE, while inhibition of ferroptosis does not seem to affect AhR signaling molecules. In summary, iron-doping with ferrocene to diesel enhanced DE-induced cardiopulmonary toxicities in chicken embryos. Ferroptosis and AhR signaling both seem to participate in this process, in which AhR signaling seems to affect ferroptosis.

Persistent metabolic toxicities following developmental exposure to hexafluoropropylene oxide trimer acid (HFPO-TA): Roles of peroxisome proliferator activated receptor gamma.

BACKGROUND: Hexafluoropropylene oxide trimer acid (HFPO-TA), a perfluorooctanoic acid (PFOA) substitute, exhibited strong affinity and capability to activate peroxisome proliferator activated receptor gamma (PPARγ), a lipid metabolism regulator, suggesting potential to induce metabolic toxicities. METHODS: Fertile chicken eggs were exposed to 0, 0.5, 1 or 2 mg/kg (egg weight) HFPO-TA and incubated until hatch. Serum from 0- and 3- month-old chickens were subjected to liquid chromatography ultra-high resolution mass spectrometry for HFPO-TA concentration, while liver, pancreas and adipose tissue samples were collected for histopathological assessments. In ovo PPARγ reporter and silencing system were established with lentivirus microinjection. qRT-PCR and immunohistochemistry were utilized to evaluate the expression levels of PPARγ downstream genes. RESULTS: In 3-month-old animals developmentally exposed to HFPO-TA, adipose tissue hyperplasia, hepatic steatosis, pancreas islet hypertrophy and elevated serum free fatty acid / insulin levels were observed. Results of reporter assay and qRT-PCR indicated HFPO-TA-mediated PPARγ transactivation in chicken embryo. Silencing of PPARγ alleviated HFPO-TA-induced changes, while PPARγ agonist rosiglitazone mimicked HFPO-TA-induced effects. qRT-PCR and immunohistochemistry revealed that FASN and GPD1 were upregulated following developmental exposure to HFPO-TA in 3-month-old animals. CONCLUSIONS: Developmental exposure to HFPO-TA induced persistent metabolic toxicities in chickens, in which PPARγ played a central role.

Long-term exposure to air pollution and risk of insulin resistance: A systematic review and meta-analysis.

OBJECTIVE: The effects of air pollution on metabolism have become a popular research topic, and a large number of studies had confirmed that air pollution exposure could induce insulin resistance (IR) to varying degrees, but the results were inconsistent, especially for the long-term exposures. The aim of the current study was to further investigate the potential effects of air pollution on IR. METHODS: A systematic review and meta-analysis of four electronic databases, including PubMed, Embase, Web of Science and Cochrane were conducted, searching for relevant studies published before June 10, 2023, in order to explore the potential relationships between long-term exposure to air pollution and IR. A total of 10 studies were included for data analysis, including seven cohort studies and three cross-sectional studies. Four major components of air pollution, including PM2.5 (particulate matter with an aerodynamic diameter of 2.5 µm or less), PM10 (particulate matter with an aerodynamic diameter of 10 µm or less), NO2, and SO2 were selected, and each analyzed for the potential impacts on insulin resistance, in the form of adjusted percentage changes in the homeostasis assessment model of insulin resistance (HOMA-IR). RESULTS: This systematic review and meta-analysis showed that for every 1 µg/m³ increase in the concentration of selected air pollutants, PM2.5 induced a 0.40% change in HOMA-IR (95%CI: -0.03, 0.84; I2 =67.4%, p = 0.009), while PM10 induced a 1.61% change (95%CI: 0.243, 2.968; I2 =49.1%, p = 0.001). Meanwhile, the change in HOMA-IR due to increased NO2 or SO2 exposure concentration was only 0.09% (95%CI: -0.01, 0.19; I2 =83.2%, p = 0.002) or 0.01% (95%CI: -0.04, 0.06; I2 =0.0%, p = 0.638), respectively. CONCLUSIONS: Long-term exposures to PM2.5, PM10, NO2 or SO2 are indeed associated with the odds of IR. Among the analyzed pollutants, inhalable particulate matters appear to exert greater impacts on IR.