Secondhand smoke alters arachidonic acid metabolism in infants and children with cystic fibrosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE107846 | GEO | 2020/12/01
REPOSITORIES: GEO
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2017-10-26 | E-MTAB-6004 | biostudies-arrayexpress
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2015-08-25 | ST000235 | MetabolomicsWorkbench
Project description:The main constituents of electronic cigarette liquids are nicotine, propylene glycol (PG), and vegetable glycerin (VG), together with distilled water and flavors. To assess the toxicity of PG/VG mixtures with and without nicotine as basic components of liquids used in e-cigarettes, a 90-day rat inhalation study according to the Organization for Economic Co-operation and Development test guideline 413 was conducted. Sprague-Dawley (SD) rats were nose-only exposed, 6 h/day, 5 days/week to filtered air, or nebulized vehicle (saline), or three concentrations of PG/VG (0.174 mg PG/l + 0.210 mg VG/l; 0.520 mg PG/l + 0.630 mg VG/l; 1.520 mg PG/l + 1.890 mg VG/l) – with (test item) and without (reference item) 23 µg nicotine/L. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared to vehicle exposure, the tested PG/VG aerosols showed only very limited biological effects with no signs of toxicity, both for the standard toxicological endpoints (e.g., histopathology, clinical chemistry) and the systems toxicological analyses (transcriptomics, proteomics, and lipidomics). The addition of nicotine to the PG/VG aerosols (23 µg/l) resulted in effects in line with nicotine effects in previous studies. These included up-regulation of xenobiotic enzymes (Cyp1a1 and Fmo3) in the lung and metabolic effects, e.g., reduction in serum lipid concentrations and changes in the expression of metabolic enzymes in the liver. Signs of a generalized stress response to nicotine exposure such as decreased thymus weights were observed; and likely, a subset of the observed metabolic alterations was interlinked with this generalized stress response. Under the conditions of this 90-day SD rat inhalation study, no toxicologically relevant effects of PG/VG aerosols (up to 1.520 mg PG/l + 1.890 mg VG/l) were observed, and the no observed adverse effect level (NOAEL) for PG/VG/nicotine was determined to be 438/544/6.7 mg/kg/day. Further the study demonstrated how complementary systems toxicology analyses can reveal, also in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine.
2017-09-11 | PXD005958 | Pride
Project description:The main constituents of electronic cigarette liquids are nicotine, propylene glycol (PG), and vegetable glycerin (VG), together with distilled water and flavors. To assess the toxicity of PG/VG mixtures with and without nicotine as basic components of liquids used in e-cigarettes, a 90-day rat inhalation study according to the Organization for Economic Co-operation and Development test guideline 413 was conducted. Sprague-Dawley (SD) rats were nose-only exposed, 6 h/day, 5 days/week to filtered air, or nebulized vehicle (saline), or three concentrations of PG/VG (0.174 mg PG/l + 0.210 mg VG/l; 0.520 mg PG/l + 0.630 mg VG/l; 1.520 mg PG/l + 1.890 mg VG/l) with (test item) and without (reference item) 23 µg nicotine/L. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared to vehicle exposure, the tested PG/VG aerosols showed only very limited biological effects with no signs of toxicity, both for the standard toxicological endpoints (e.g., histopathology, clinical chemistry) and the systems toxicological analyses (transcriptomics, proteomics, and lipidomics). The addition of nicotine to the PG/VG aerosols (23 µg/l) resulted in effects in line with nicotine effects in previous studies. These included up-regulation of xenobiotic enzymes (Cyp1a1 and Fmo3) in the lung and metabolic effects, e.g., reduction in serum lipid concentrations and changes in the expression of metabolic enzymes in the liver. Signs of a generalized stress response to nicotine exposure such as decreased thymus weights were observed; and likely, a subset of the observed metabolic alterations was interlinked with this generalized stress response. Under the conditions of this 90-day SD rat inhalation study, no toxicologically relevant effects of PG/VG aerosols (up to 1.520 mg PG/l + 1.890 mg VG/l) were observed, and the no observed adverse effect level (NOAEL) for PG/VG/nicotine was determined to be 438/544/6.7 mg/kg/day. Further the study demonstrated how complementary systems toxicology analyses can reveal, also in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine.
2017-09-11 | PXD006894 | Pride
Project description:The main constituents of electronic cigarette liquids are nicotine, propylene glycol (PG), and vegetable glycerin (VG), together with distilled water and flavors. To assess the toxicity of PG/VG mixtures with and without nicotine as basic components of liquids used in e-cigarettes, a 90-day rat inhalation study according to the Organization for Economic Co-operation and Development test guideline 413 was conducted. Sprague-Dawley (SD) rats were nose-only exposed, 6 h/day, 5 days/week to filtered air, or nebulized vehicle (saline), or three concentrations of PG/VG (0.174 mg PG/l + 0.210 mg VG/l; 0.520 mg PG/l + 0.630 mg VG/l; 1.520 mg PG/l + 1.890 mg VG/l) – with (test item) and without (reference item) 23 µg nicotine/L. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared to vehicle exposure, the tested PG/VG aerosols showed only very limited biological effects with no signs of toxicity, both for the standard toxicological endpoints (e.g., histopathology, clinical chemistry) and the systems toxicological analyses (transcriptomics, proteomics, and lipidomics). The addition of nicotine to the PG/VG aerosols (23 µg/l) resulted in effects in line with nicotine effects in previous studies. These included up-regulation of xenobiotic enzymes (Cyp1a1 and Fmo3) in the lung and metabolic effects, e.g., reduction in serum lipid concentrations and changes in the expression of metabolic enzymes in the liver. Signs of a generalized stress response to nicotine exposure such as decreased thymus weights were observed; and likely, a subset of the observed metabolic alterations was interlinked with this generalized stress response. Under the conditions of this 90-day SD rat inhalation study, no toxicologically relevant effects of PG/VG aerosols (up to 1.520 mg PG/l + 1.890 mg VG/l) were observed, and the no observed adverse effect level (NOAEL) for PG/VG/nicotine was determined to be 438/544/6.7 mg/kg/day. Further the study demonstrated how complementary systems toxicology analyses can reveal, also in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine.
2017-09-11 | PXD005959 | Pride
Project description:Aspergillus fumigatus contributes to invasive and allergic pulmonary disease in immunocompromised individuals. The pulmonary mucus of cystic fibrosis (CF) patients displays elevated levels of the pleiotropic cathelicidin antimicrobial peptide LL-37 and the aim of this work was to assess the effect of LL-37 on the growth A. fumigatus. Exposure of A. fumigatus conidia to high concentrations of intact LL-37 (100 μg/ml) for 24 hours had a positive effect on growth (277.45 ± 22.59% (p < 0.01)) whereas scrambled LL-37 (76.45 ± 7.46%) did not. Exposure of 24 hour pre-formed mycelium to 5 μg/ml LL-37 for 48 hours increased hyphal wet weight significantly (4.37 ± 0.23 g, p < 0.001) compared to the control (2.67 ± 0.05 g). Amino acid leakage from mycelium was observed in the presence of LL-37 and gliotoxin secretion was increased at 24 hours from LL-37 exposed hyphae (169.1 ± 6.36 ng/mg hyphae, p < 0.05) compared to the control (102 ± 18.81 ng/mg hyphae). Quantitative proteomic analysis of 24 hour LL-37 treated hyphae revealed an increase in the abundance of proteins associated with growth (eIF-5A (16.3 fold increased), tissue degradation (aspartic endopeptidase (4.7 fold increased)) and allergic reactions (Asp F13 (10 fold increased)). By 48 hours there was an increase in proteins indicative of cellular stress (glutathione peroxidase (9 fold increased)), growth (eIF-5A (6 fold increased), and virulence (ribonuclease mitogillin (3.7 fold increased). These results indicate that LL-37 stimulates A. fumigatus growth and this may result in increased fungal growth and secretion of toxins in the lungs of CF patients.
2018-05-22 | PXD008143 | Pride
Project description:The main constituents of electronic cigarette liquids are nicotine, propylene glycol (PG), and vegetable glycerin (VG), together with distilled water and flavors. To assess the toxicity of PG/VG mixtures with and without nicotine as basic components of liquids used in e-cigarettes, a 90-day rat inhalation study according to the Organization for Economic Co-operation and Development test guideline 413 was conducted. Sprague-Dawley (SD) rats were nose-only exposed, 6?h/day, 5 days/week to filtered air, or nebulized vehicle (saline), or three concentrations of PG/VG (0.174 mg PG/l + 0.210 mg VG/l; 0.520 mg PG/l + 0.630 mg VG/l; 1.520 mg PG/l + 1.890 mg VG/l) � with (test item) and without (reference item) 23 �g nicotine/L. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared to vehicle exposure, the tested PG/VG aerosols showed only very limited biological effects with no signs of toxicity, both for the standard toxicological endpoints (e.g., histopathology, clinical chemistry) and the systems toxicological analyses (transcriptomics, proteomics, and lipidomics). The addition of nicotine to the PG/VG aerosols (23 �g/l) resulted in effects in line with nicotine effects in previous studies. These included up-regulation of xenobiotic enzymes (Cyp1a1 and Fmo3) in the lung and metabolic effects, e.g., reduction in serum lipid concentrations and changes in the expression of metabolic enzymes in the liver. Signs of a generalized stress response to nicotine exposure such as decreased thymus weights were observed; and likely, a subset of the observed metabolic alterations was interlinked with this generalized stress response. Under the conditions of this 90-day SD rat inhalation study, no toxicologically relevant effects of PG/VG aerosols (up to 1.520 mg PG/l + 1.890 mg VG/l) were observed, and the no observed adverse effect level (NOAEL) for PG/VG/nicotine was determined to be 438/544/6.7 mg/kg/day. Further the study demonstrated how complementary systems toxicology analyses can reveal, also in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine.
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