Pulmonary effects of inhaled diesel particles in rats
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE152720 | GEO | 2022/12/31
REPOSITORIES: GEO
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Project description:The pulmonary inflammatory response to inhalation exposure to fracking sand dust (FSD) was investigated in a rat model. Adult male Sprague-Dawley rats were exposed by whole-body inhalation to air or an aerosol of FSD at concentrations of 10 or 30 mg/m3, 6 hours/day for 4 days. The control and FSD-exposed rats were euthanized at post-exposure time intervals of 1, 7 or 27days and pulmonary inflammatory, cytotoxic and oxidant responses were determined. Deposition of FSD particles was detected in the lungs of all the FSD-exposed rats. Analysis of bronchoalveolar lavage parameters of toxicity, oxidant generation, and inflammation did not reveal any significant persistent pulmonary toxicity in the FSD- exposed rats. Similarly, the lung histology of the FSD-exposed rats showed only minimal changes in influx of macrophages following the exposure. Determination of global gene expression profiles detected significant differential expressions of only six and five genes in the 10 mg/m3, 1 day post-exposure, and the 30 mg/m3, 7-day post-exposure FSD groups, respectively. Taken together, data obtained from the present study demonstrated that FSD inhalation exposure resulted in minimal/no toxicity or gene expression changes in the lungs of the rats.
2020-10-01 | GSE148255 | GEO
Project description:DEP exposure is linked to increases in cardiovascular effects. This effect is enhanced in individuals with pre-existing disease. Animal models of cardiovascular disease are used to study this susceptibility. The heart is rich in mitochondria, which produce high levels of free radicals, leading to inactivation of tricarboxylic acid cycle enzymes. We hypothesized that a 4-wk DEP inhalation would result in strain-related structural impairment of cardiac mitochondria and changes in these enzyme activities in WKY and SHR. Male rats (12-14 wks age) were exposed whole body to air or 0.5 or 2.0 mg/m3 DEP for 6h/d, 5 d/wk for 4 wks. Neutrophilic influx was noted in the bronchoalveolar lavage fluid in both strains. A slightly lower level of baseline cardiac mitochondrial aconitase activity was seen in SHR than WKY. Aconitase activity appeared to be decreased in an exposure related manner in both strains. Significantly higher baseline levels of cardiac cytosolic ferritin and aconitase activity were seen in the SHR than WKY. No exposure-related changes were noted in either of these measures. Mitochondrial succinate and isocitrate dehydrogenase activities were not changed following DEP exposure in either strain. Transmission electron microscopy images of the heart indicated abnormalities in cardiac mitochondria of control SHR but not control WKY. No exposure related ultrastructural changes were induced by DEP in either strain. In conclusion, strain differences in cardiac biomarkers of oxidative stress and structure of mitochondria exist between SHR and WKY. DEP exposure results in small changes in cardiac mitochondrial and cytosolic markers of oxidative stress. (Abstract does not represent USEPA policy.) Experiment Overall Design: Two strains of rats (Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats were exposed to either diesel exhaust particles or clean air. Four biological replicates were used for each strain/treatment exposure. Total number of chips equals 16.
2008-10-20 | E-GEOD-9694 | biostudies-arrayexpress
Project description:Epidemiological studies have linked exposure to ambient particulate matter (PM) with increased asthmatic symptoms. Diesel exhaust particles (DEP) are a predominant source of vehicle derived ambient PM, and experimental studies have demonstrated that they may have adjuvant potential when given with an antigen. We previously compared 3 DEP samples: N-DEP, A-DEP, and C-DEP in a murine ovalbumin (OVA) mucosal sensitization model and reported the adjuvant activity to be: C-DEP ? A-DEP > N-DEP. The present study analyzed gene expression changes from the lungs of these mice. Transcription profiling demonstrated that all the DEP samples altered cytokine and toll-like receptor pathways regardless of type, with or without antigen sensitization. Further analysis of DEP exposure with OVA showed that all DEP treatments altered networks involved in immune and inflammatory responses. The A- and C-DEP/OVA treatments induced differential expression of apoptosis pathways in association with stronger adjuvant responses, while expression of cell cycle control and DNA damage pathways were also altered in the C-DEP/OVA treatment. This comprehensive approach using gene expression analysis to examine changes at a pathway level provides detailed information on events occurring in the lung after DEP exposure, and confirms that the most bioactive sample induced many more individual genes and changes in immuno-regulatory and homeostatic pathways. Female BALB/C mice (8-10 weeks old) were randomly divided into 8 treatment groups containing 3 mice each and exposed to saline, 20 ug ovalbumin, 150 ug diesel exhaust particles (either C-DEP, A-DEP, or N-DEP), or diesel exhaust particles + ovalbumin by intranasal instillation on Days 0 and 13 and necropsied 18 hrs latter.
2010-07-10 | E-GEOD-22357 | biostudies-arrayexpress
Project description:The lung response to inhalation exposure to oil vapor particles was investigated in a rat model. Adult male Sprague-Dawley rats were exposed by whole-body inhalation to air or an aerosol containing oil vapor particles at concentrations of 300 ppm, 6 hours/day for 1 day (shot-term) or 300 ppm, 6 hours/day, 4 days/week for 4 weeks (long-term). The control and oil vapor exposed rats were euthanized at post-exposure time intervals of 1 and 28 days and lung toxicity determined. Analysis of bronchoalveolar lavage parameters of toxicity such as lactate dehydrogenase activity, oxidant generation, and inflammation did not reveal any significant lung toxicity in the oil vapor exposed rats. Approximately 50 genes each were found significantly differentially expressed in both the short- and long-term exposure groups of the rats at the one-day post-exposure time interval. The data obtained from the present study demonstrated that oil vapor inhalation exposure, under the exposure conditions employed in the present study, did not result in any significant lung toxicity in the rats despite the gene expression changes detected.
2022-12-31 | GSE152187 | GEO
Project description:Occupational exposure to crystalline silica results in serious health effects, most notably, silicosis and cancer. A proper understanding of the mechanism(s) underlying the initiation and progression of silica-induced pulmonary toxicity is critical for the intervention and/or prevention of the adverse health effects associated with crystalline silica exposure. Rats were exposed to crystalline silica by inhalation at a concentration of 15 mg/m3, 6 hours/day, 5 days/week for 3, 6 or 12 weeks. At the end of each exposure time point, toxicity and global gene expression changes were determined in the lungs. In general, silica exposure resulted in pulmonary toxicity that was dependent on the duration of silica exposure. A significant and silica exposure time-dependent increase in lactate dehydrogenase activity and accumulation of alveolar macrophages and infiltrating neutrophils in the bronchoalveolar lavage fluid suggested crystalline silica-induced pulmonary toxicity in the rats. Histological changes indicative of pulmonary toxicity were detectable only in the lungs of rats that were exposed to silica for 6- or 12-weeks. Minimal, sub-acute pulmonary inflammation consisting mainly of macrophage accumulation and infiltration of neutrophils was seen in 2 out of 8 rats in the 6-week silica exposure group. Chronic active inflammation, type II pneumocyte hyperplasia, and fibrosis were detected following 12-weeks of silica exposure in all rat lungs. In addition, crystalline silica was visible in the lungs of the rats belonging to the 12-week exposure group. A significant increase in the number of neutrophils seen in the blood indicated silica-induced systemic inflammation in the rats. Microarray analysis of the global gene expression profiles of the rat lungs detected significant differential expression (FDR p <0.05 and fold change >1.5) of 38, 77 and 99 genes in the rats exposed to silica for 3-, 6- and 12-weeks, respectively, compared to the time-matched controls. Bioinformatics analysis of the differentially expressed genes identified significant enrichment of functions, networks and pathways related to inflammation, cancer, oxidative stress, fibrosis and tissue remodeling in the lungs of the silica exposed rats. Collectively, the results of our study provided insights into the molecular mechanisms underlying pulmonary toxicity following sub-chronic exposure to silica in rats. 36 samples were analyzed in this experiment. 6 rats were exposed to crystalline silica by inhalation 15 mg/m3, 6 hours/day, 5 days, 3 weeks. 6 rats were exposed to crystalline silica by inhalation 15 mg/m3, 6 hours/day, 5 days, 6 weeks. 6 rats were exposed to crystalline silica by inhalation 15 mg/m3, 6 hours/day, 5 days, 12 weeks. 18 rats served as controls (6 for each 3 week, 6 week, and 12 week exposure) and were exposed to air during treatment times. Lung gene expression profiling was performed using RNA isolated from rat lung samples.
2014-07-01 | E-GEOD-49144 | biostudies-arrayexpress
Project description:Air pollution is an environmental risk factor linked to multiple human diseases including cardiovascular diseases (CVDs). While particulate matter (PM) emitted by diesel exhaust damages multiple organ systems, heart disease is one of the most severe pathologies affected by PM. However, the in vivo effects of diesel exhaust particles (DEP) on the heart and the molecular mechanisms of DEP-induced heart dysfunction have not been investigated. In the current study, we attempted to identify the proteomic signatures of heart fibrosis caused by diesel exhaust particles (DEP) in CVDs-prone apolipoprotein E knockout (ApoE-/-) mice model using tandem mass tag (TMT)-based quantitative proteomic analysis. DEP exposure induced mild heart fibrosis in ApoE-/- mice compared with severe heart fibrosis in ApoE-/- mice that were treated with CVDs-inducing peptide, angiotensin II. TMT-based quantitative proteomic analysis of heart tissues between PBS- and DEP-treated ApoE-/- mice revealed significant upregulation of proteins associated with platelet activation and TGFβ-dependent pathways. Our data suggest that DEP exposure could induce heart fibrosis, potentially via platelet-related pathways and TGFβ induction, causing cardiac fibrosis and dysfunction.
2023-12-09 | PXD045029 | Pride
Project description:From an occupational standpoint, exposure to silica can have devastating consequences. An estimated 2.3 million workers in the U.S. are exposed to dust containing crystalline silica, annually. In addition, of the 140 million people over the age of 20, employed in the U.S., 30% are obese. If and how diet-induced obesity modifies silica-induced pulmonary toxicity is unknown. Therefore, the objective of this study was to determine the effect of diet-induced obesity, if any, on silica induced pulmonary toxicity. Rats (Fischer 344, male) were fed either a regular-fat diet (RFD; 18% kcal as fat) (Envigo, Indianapolis, IN) or a high-fat diet (HFD; 60% kcal as fat) (Envigo, Indianapolis, IN) and exposed by whole-body inhalation to either air or crystalline silica (15 mg/m3, 6 hours/day, 5 days). At designated post-exposure time intervals (1, 3, 6, and 9 months), pulmonary toxicity was determined. Silica inhalation resulted in pulmonary toxicity, which progressed across all post-exposure time points, as evidenced by enhanced neutrophil infiltration, increased LDH levels, enhanced oxidant production, and increased inflammatory cytokine levels. The incidence and severity of silica-induced lung pathology was similar between the two diet groups up to 6 months post-exposure. However, by 9 months post-exposure, silica-induced pathology tended to be slightly more severe in animals fed an RFD compared to those fed an HFD. Lung gene expression profiles were then determined in the rats euthanized at the 3- and 9-month post-silica exposure time intervals by RNA sequencing to identify transcript differences between the two timepoints.
2022-12-31 | GSE142446 | GEO
Project description:The potential of diesel exhaust particles (DEP) to transform human bronchial epithelial cells (HBEC3) was investigated and a stably transformed cell line (T2-HBEC3) was established. Short-term DEP exposure experiments adds information of immunomodulatory effect markers and differences in susceptibility between normal and sensitized bronhial epithelial cells of the human lung.
2017-11-30 | GSE107481 | GEO
Project description:The present research aimed to investigate peripheral blood gene expression profiling as a minimally invasive surrogate approach to study silica-induced pulmonary toxicity. Rats were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days). Pulmonary damage and blood gene expression profiles were determined at various latency periods (0 - 16 weeks). Silica exposure resulted in pulmonary toxicity and this was evidenced by histological changes in the lungs and elevation of LDH activity, and total protein and albumin contents in the bronchoalveolar lavage fluid (BALF) of the rats. Microarray analysis of global gene expression profiles in the blood of the rats identified genes that were differentially expressed in response to silica exposure and toxicity. The number of significantly differentially expressed genes in the blood of silica exposed rats correlated with the severity of silica-induced pulmonary toxicity. Genes involved in biological functions such as inflammatory response, cancer, pulmonary damage, oxidative stress, energy metabolism, fibrosis, etc, were found differentially expressed in the blood of the silica exposed rats compared with the controls. Induction of pulmonary inflammation in the silica exposed rats, as suggested by differential expression of inflammatory response genes in the blood, was supported by significant increases in the number of macrophages and infiltrating neutrophils as well as the activity of pro-inflammatory chemokines M-bM-^@M-^S MCP1 and MIP2, observed in the BALF of the silica exposed rats. A silica-responsive blood gene expression signature developed using the gene expression data predicted with significant accuracy the exposure of rats to lower concentrations (1 and 2 mg/m3) of silica. Taken together our findings suggest the potential application of peripheral blood gene expression profiling as a minimally invasive and efficient surrogate approach to detect and study silica-induced pulmonary toxicity. 96 samples were analyzed in this experiment. The RNA from rat blood samples was isolated for gene expression studies. Rats (48) were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days) and air (24). Blood gene expression profiling was performed using rat blood samples, 8 each for silica exposed and 4 each for air exposed controls at various post-exposure time periods (0, 1, 2, 4, 8, and 16 weeks). A silica-responsive blood gene expression signature was developed using the gene expression data obtained from the 0 week post-exposure group and the control rats. The signature was tested for predicting silica exposure and resulting toxicity in the rats exposed to lower concentrations (1 and 2 mg/m3) of silica (8 rats per group) and air (8 rats).
2011-12-02 | E-GEOD-27023 | biostudies-arrayexpress
Project description:DEP exposure is linked to increases in cardiovascular effects. This effect is enhanced in individuals with pre-existing disease. Animal models of cardiovascular disease are used to study this susceptibility. The heart is rich in mitochondria, which produce high levels of free radicals, leading to inactivation of tricarboxylic acid cycle enzymes. We hypothesized that a 4-wk DEP inhalation would result in strain-related structural impairment of cardiac mitochondria and changes in these enzyme activities in WKY and SHR. Male rats (12-14 wks age) were exposed whole body to air or 0.5 or 2.0 mg/m3 DEP for 6h/d, 5 d/wk for 4 wks. Neutrophilic influx was noted in the bronchoalveolar lavage fluid in both strains. A slightly lower level of baseline cardiac mitochondrial aconitase activity was seen in SHR than WKY. Aconitase activity appeared to be decreased in an exposure related manner in both strains. Significantly higher baseline levels of cardiac cytosolic ferritin and aconitase activity were seen in the SHR than WKY. No exposure-related changes were noted in either of these measures. Mitochondrial succinate and isocitrate dehydrogenase activities were not changed following DEP exposure in either strain. Transmission electron microscopy images of the heart indicated abnormalities in cardiac mitochondria of control SHR but not control WKY. No exposure related ultrastructural changes were induced by DEP in either strain. In conclusion, strain differences in cardiac biomarkers of oxidative stress and structure of mitochondria exist between SHR and WKY. DEP exposure results in small changes in cardiac mitochondrial and cytosolic markers of oxidative stress. (Abstract does not represent USEPA policy.) Keywords: strain differences, exposure differences
2008-06-23 | GSE9694 | GEO