The Acute Effect of Diesel Exhaust Particles and Different Fractions Exposure on Blood Coagulation Function in Mice.

The toxicity and widespread exposure opportunity of diesel exhaust particles (DEP) has aroused public health concerns. This study aimed to investigate the acute effect of DEP and different fractions exposure on blood coagulation function in mice. In this study, nine- week-old C57BL/6J male mice were divided into four exposure groups (with 15 mice in each group). The water-soluble (WS) and water-insoluble (WIS) fractions of DEP were isolated, and intratracheal instillation was used for DEP, WS and WIS exposure. The phosphate buffer saline (PBS) exposure group was set as the control group. After 24 h exposure, the mice were sacrificed for blood routine, coagulation function and bleeding time examinations to estimate the acute effect of DEP, WS and WIS exposure on the blood coagulation function. In our results, no statistically significant difference in weight of body, brain and lung was observed in different exposure groups. While several core indexes in blood coagulation like bleeding time (BT), fibrinogen (FIB), activated partial thromboplastin time (APTT) and prothrombin time (PT) altered or showed a lower tendency after DEP, WS and WIS exposure. For example, BT was lower In WIS exposure group (211.00 s) compared with PBS exposure group (238.50 s) (p < 0.01), and FIB was lower in WS exposure group (233.00 g/L) compared with PBS exposure group (249.50 g/L) (p < 0.05). Additionally, systemic inflammation-related indexes like white blood cell count (WBC), neutrophil count (NEUT), lymphocyte count (LYMPH) altered after DEP, WS and WIS exposure. In conclusion, DEP, WS and WIS fractions exposure could result in the hypercoagulable state of blood in mice. The noteworthy effects of WS and WIS fractions exposure on blood coagulation function deserve further investigation of the potential mechanism.

Exposure to different fractions of diesel exhaust PM2.5 induces different levels of pulmonary inflammation and acute phase response.

AIM: Ambient fine particulate matter (PM2.5) consists of various components, and their respective contributions to the toxicity of PM2.5 remains to be determined. To provide specific recommendations for preventing adverse effects due to PM2.5 pollution, we determined whether the induction of pulmonary inflammation, the putative pathogenesis for the morbidity and mortality due to PM2.5 exposure, was fractioned through solubility-dependent fractioning. METHODS: In the present study, the water and heptane solubilities-dependent serial fractioning of diesel exhaust particulate matter (DEP), a prominent source of urban PM2.5 pollution, was performed. The pro-inflammatory actions of these resultant fractions were then determined using both an intratracheal instillation mouse model and cultured BEAS-2B cells, a human bronchial epithelial cell line. RESULTS: Instillation of the water-insoluble, but not -soluble fraction elicited significant pulmonary inflammatory and acute phase responses, comparable to those induced by instillation of DEP. The water-insoluble fraction was further fractioned using heptane, a polar organic solvent, and instillation of heptane-insoluble, but not -soluble fraction elicited significant pulmonary inflammation and acute phase responses. Furthermore, we showed that DEP and water-insoluble DEP, but not water-soluble DEP, activated pro-inflammatory signaling in cultured BEAS-2B cells, ruling out the possibility that the solubility impacts the in vivo distribution and thus the pulmonary inflammatory response.

Developmental programming of obesity by maternal exposure to concentrated ambient PM2.5 is maternally transmitted into the third generation in a mouse model.

BACKGROUND: Obesity is an uncontrolled global epidemic and one of the leading global public health challenges. Maternal exposure to ambient fine particulate matter (PM2.5) may adversely program offspring's adiposity, suggesting a specialized role of PM2.5 pollution in the global obesity epidemic. However, the vulnerable window for this adverse programming and how it is cross-generationally transmitted have not been determined. Therefore, in the present study, female C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during different periods, and the development and adulthood adiposity of their four-generational offspring were assessed. RESULTS: Our data show that the pre-conceptional but not gestational exposure to CAP was sufficient to cause male but not female offspring's low birth weight, accelerated postnatal weight gain, and increased adulthood adiposity. These adverse developmental traits were transmitted into the F2 offspring born by the female but not male F1 offspring of CAP-exposed dams. In contrast, no adverse development was noted in the F3 offspring. CONCLUSIONS: The present study identified a pre-conceptional window for the adverse programming of adiposity by maternal exposure to PM2.5, and showed that it was maternally transmitted into the third generation. These data not only call special attention to the protection of women from exposure to PM2.5, but also may facilitate the development of intervention to prevent this adverse programming.

Metabolomics analysis of a mouse model for chronic exposure to ambient PM2.5.

Chronic ambient fine particulate matter (PM2.5) exposure correlates with various adverse health outcomes. Its impact on the circulating metabolome-a comprehensive functional readout of the interaction between an organism's genome and environment-has not however been fully understood. This study thus performed metabolomics analyses using a chronic PM2.5 exposure mouse model. C57Bl/6J mice (female) were subjected to inhalational concentrated ambient PM2.5 (CAP) or filtered air (FA) exposure for 10 months. Their sera were then analyzed by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). These analyses identified 2570 metabolites in total, and 148 of them were significantly different between FA- and CAP-exposed mice. The orthogonal partial least-squares discriminant analysis (OPLS-DA) and heatmap analyses displayed evident clustering of FA- and CAP-exposed samples. Pathway analyses identified 6 perturbed metabolic pathways related to amino acid metabolism. In contrast, biological characterization revealed that 71 differential metabolites were related to lipid metabolism. Furthermore, our results showed that CAP exposure increased stress hormone metabolites, 18-oxocortisol and 5a-tetrahydrocortisol, and altered the levels of circadian rhythm biomarkers including melatonin, retinal and 5-methoxytryptophol.

Exposure to concentrated ambient PM2.5 alters the composition of gut microbiota in a murine model.

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) correlates with abnormal glucose homeostasis, but the underlying biological mechanism has not been fully understood. The gut microbiota is an emerging crucial player in the homeostatic regulation of glucose metabolism. Few studies have investigated its role in the PM2.5 exposure-induced abnormalities in glucose homeostasis. METHODS: C57Bl/6J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) for 12 months using a versatile aerosol concentration enrichment system (VACES) that was modified for long-term whole-body exposures. Their glucose homeostasis and gut microbiota were examined and analysed by correlation and mediation analysis. RESULTS: Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) showed that CAP exposure markedly impaired their glucose and insulin tolerance. Faecal microbiota analysis demonstrated that the impairment in glucose homeostasis was coincided with decreased faecal bacterial ACE and Chao-1 estimators (the indexes of community richness), while there was no significant change in all faecal fungal alpha diversity estimators. The Pearson's correlation analyses showed that the bacterial richness estimators were correlated with glucose and insulin tolerance, and the mediation analyses displayed a significant mediation of CAP exposure-induced glucose intolerance by the alteration in the bacterial Chao-1 estimator. LEfSe analyses revealed 24 bacterial and 21 fungal taxa differential between CAP- and FA-exposed animals. Of these, 14 and 20 bacterial taxa were correlated with IPGTT AUC and ITT AUC, respectively, and 5 fungal taxa were correlated with abnormalities in glucose metabolism. CONCLUSIONS: Chronic exposure to PM2.5 causes gut dysbiosis and may subsequently contribute to the development of abnormalities in glucose metabolism.