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Toxicology Letters Feb 2024Tobacco smoke contains various carcinogenic ingredients such as nicotine, acrolein, and benzopyrene; however, their effects on cancer treatment are not fully understood....
Tobacco smoke contains various carcinogenic ingredients such as nicotine, acrolein, and benzopyrene; however, their effects on cancer treatment are not fully understood. Claudin-1 (CLDN1), a component of tight junctions, is involved in the increased resistance to anticancer drugs. In this study, we found that acrolein increases the mRNA and protein levels of CLDN1 in RERF-LC-AI cells derived from human lung squamous cell carcinoma (SCC). Acrolein increased the p-extracellular signal-regulated kinase (ERK) 1/2 levels without affecting the p-Akt level. The acrolein-induced elevation of CLDN1 expression was attenuated by U0126, a mitogen-activated protein kinase kinas (MEK) inhibitor. These results indicate that the activation of MEK/ERK pathway is involved in the acrolein-induced elevation of CLDN1 expression. In a spheroid model, acrolein suppressed the accumulation and toxicity of doxorubicin (DXR), which were rescued by CLDN1 silencing. The acrolein-induced effects were also observed in lung SCC-derived EBC-1 and LK-2 cells. Acrolein also increased the expression level of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that regulates antioxidant and detoxifying genes, which were inhibited by CLDN1 silencing. In spheroid cells, the levels of reactive oxygen species were enhanced by acrolein, which was inhibited by CLDN1 silencing. Taken together, acrolein may reduce the anticancer drug-induced toxicity in human lung SCC cells mediated by high CLDN1 expression followed by the upregulation of Nrf2 signaling pathway.
Topics: Humans; Claudin-1; NF-E2-Related Factor 2; Acrolein; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Carcinoma, Squamous Cell; Lung Neoplasms; Lung; Mitogen-Activated Protein Kinase Kinases
PubMed: 38142011
DOI: 10.1016/j.toxlet.2023.12.012 -
Environmental Science and Pollution... May 2024Two commercial biopesticides were studied to determine their persistence in two soil types, such as sandy clay loam and clay loam soils. For this purpose, an orange...
Two commercial biopesticides were studied to determine their persistence in two soil types, such as sandy clay loam and clay loam soils. For this purpose, an orange oil-based biopesticide was used, being limonene its main ingredient. The other biopesticide was based on cinnamon extract and trans-cinnamaldehyde as its main component. Degradation of these compounds was monitored, and transformation products or metabolites were detected. Limonene and its metabolites were analyzed by gas chromatography (GC) and trans-cinnamaldehyde by ultra-high-performance liquid chromatography (UHPLC). Both techniques were coupled to a high-resolution mass (HRMS) analyzer, such as quadrupole (Q)-Orbitrap. Limonene and trans-cinnamaldehyde were rapidly degraded as result of first-order kinetics. Possible metabolites such as thymol, cymene, isoterpinolene and cymenene for limonene, and hydroxycinnamic acid for trans-cinnamaldehyde were tentatively identified. Moreover, four other metabolites of trans-cinnamaldehyde, some of them not previously described, were also detected.
Topics: Limonene; Acrolein; Chromatography, High Pressure Liquid; Soil; Soil Pollutants; Terpenes; Cyclohexenes
PubMed: 38668941
DOI: 10.1007/s11356-024-33334-6 -
Journal of Exposure Science &... Dec 2023Gasoline-powered vehicles and equipment are an important source of air pollution in California. Many gasoline-related pollutants pose significant health concerns. The...
BACKGROUND
Gasoline-powered vehicles and equipment are an important source of air pollution in California. Many gasoline-related pollutants pose significant health concerns. The California Air Resources Board strictly regulates the state's gasoline formulation and vehicle emissions.
OBJECTIVE
To investigate exposure trends for gasoline-related air pollutants between 1996 and 2014, capturing the period before and after the removal of methyl t-butyl ether (MTBE).
METHODS
We identified gasoline-related chemicals with known or suspected health concerns and adequate ambient air monitoring data. Average exposures to the general public were estimated from 1996 to 2014 in five major air basins and statewide. We determined the fractions of exposures attributable to gasoline use and evaluated cancer and non-cancer risks for chemicals with available cancer potencies and health reference values.
RESULTS
We found that average gasoline-attributable cancer risks for the general California population from the most highly emitted carcinogens (acetaldehyde, benzene, 1,3-butadiene, and formaldehyde) declined by over 80% between 1996 and 2014. This decline occurred despite roughly constant statewide gasoline sales, an increase in vehicle miles traveled, and an approximately 10% increase in vehicle registrations over this same period. Naphthalene, measured as a volatile organic compound (VOC), was the most abundant gasoline-related polycyclic aromatic hydrocarbon (PAH). From 1996 to 2014, gasoline-attributable cancer risks for naphthalene were estimated to drop approximately threefold in the South Coast Air Basin. Exposures to gasoline-related chemicals associated with non-cancer health effects, such as chronic respiratory toxicity or neurotoxicity, were generally below levels of concern. The exception was acrolein, with gasoline-related exposures in 2014 estimated to be high enough to pose risks for respiratory toxicity.
IMPACT STATEMENT
Our historical analysis demonstrated the success of California's regulatory efforts to reduce gasoline-related air pollutant exposures and risks to the general public. New efforts are focused on addressing gasoline-related and other air pollution in heavily impacted communities affected by multiple environmental and social stressors.
PubMed: 38066330
DOI: 10.1038/s41370-023-00615-0 -
Environmental Science & Technology... Aug 2023On February 3, 2023, a train carrying numerous hazardous chemicals derailed in East Palestine, OH, spurring temporary evacuation of residents and a controlled burn of...
On February 3, 2023, a train carrying numerous hazardous chemicals derailed in East Palestine, OH, spurring temporary evacuation of residents and a controlled burn of some of the hazardous cargo. Residents reported health symptoms, including headaches and respiratory, skin, and eye irritation. Initial data from U.S. Environmental Protection Agency (EPA) stationary air monitors indicated levels of potential concern for air toxics based on hazard quotient calculations. To provide complementary data, we conducted mobile air quality sampling on February 20 and 21 using proton transfer reaction-mass spectrometry. Measurements were taken at 1 s intervals along routes designed to sample both close to and farther from the derailment. Mobile air monitoring indicated that average concentrations of benzene, toluene, xylenes, and vinyl chloride were below minimal risk levels for intermediate and chronic exposures, similar to EPA stationary monitoring data. Levels of acrolein were high relative to those of other volatile organic compounds, with spatial analyses showing levels in East Palestine up to 6 times higher than the local rural background. Nontargeted analyses identified levels of additional unique compounds above background levels, some displaying spatiotemporal patterns similar to that of acrolein and others exhibiting distinct hot spots. These initial findings warrant follow-up mobile air quality monitoring to characterize longitudinal exposure and risk levels.
PubMed: 37577363
DOI: 10.1021/acs.estlett.3c00324 -
Naunyn-Schmiedeberg's Archives of... Mar 2024Acrolein, a common environmental pollutant, is linked to the development of cardiovascular inflammatory diseases. Pelargonidin is a natural compound with...
Acrolein, a common environmental pollutant, is linked to the development of cardiovascular inflammatory diseases. Pelargonidin is a natural compound with anti-inflammation activity. In this study, we aimed to explore the effects of pelargonidin on inflammation induced by acrolein in human umbilical vein endothelial cells (HUVECs). MTT assay was utilized for assessing cell viability in HUVECs. LDH release in HUVECs was measured using the LDH kit. Western blot was used to detect the protein expression of p-p65, p65 and COX-2. Inflammation was evaluated through determining the levels of PGE2, IL-1β, IL-6, IL-8 and TNF-α in HUVECs after treatment. COX-2 mRNA expression and COX-2 content were examined using RT-qPCR and a human COX-2 ELISA kit, respectively. Acrolein treatment at 50 μM resulted in a 45% decrease in the viability and an increase in LDH release (2.2-fold) in HUVECs. Pelargonidin at 5, 10, 20, and 40 μM alleviated acrolein-caused inhibitory effect on cell viability (increased to 1.3-, 1.5-, 1.8-, and 1.9-fold, respectively, compared to acrolein treatment group) and promoting effect on LDH release (decreased to 82%, 75%, 62%, and 58%, respectively, compared to acrolein treatment group) in HUVECs. Moreover, pelargonidin or pyrrolidine dithiocarbamate (PDTC; an NF-κB pathway inhibitor) inhibited acrolein-induced activation of the NF-κB pathway. Acrolein elevated the levels of PGE2, IL-1β, IL-6, IL-8 and TNF-α (from 40.2, 27.3, 67.2, 29.0, 24.8 pg/mL in control group to 224.0, 167.3, 618.3, 104.6, and 275.1 pg/mL in acrolein treatment group, respectively), which were retarded after pelargonidin (decreased to 134.8, 82.3, 246.2, 70.2, and 120.8 pg/mL in acrolein + pelargonidin treatment group) or PDTC (decreased to 107.9, 80.1, 214.6, 64.0, and 96.6 pg/mL in acrolein + PDTC treatment group) treatment in HUVECs. Pelargonidin inactivated the NF-κB pathway to reduce acrolein-induced COX-2 expression. Furthermore, pelargonidin relieved acrolein-triggered inflammation through decreasing COX-2 expression by inactivating the NF-κB pathway in HUVECs. In conclusion, pelargonidin could protect against acrolein-triggered inflammation in HUVECs through attenuating COX-2 expression by inactivating the NF-κB pathway.
Topics: Humans; NF-kappa B; Human Umbilical Vein Endothelial Cells; Cyclooxygenase 2; Acrolein; Tumor Necrosis Factor-alpha; Interleukin-6; Interleukin-8; Dinoprostone; Signal Transduction; Cells, Cultured; Inflammation; Anthocyanins; Proline; Thiocarbamates
PubMed: 37728621
DOI: 10.1007/s00210-023-02712-1 -
Advanced Healthcare Materials Apr 2024A high level of reduced glutathione is a major factor contributing to the radioresistance observed in solid tumors. To address this radioresistance associated with...
A high level of reduced glutathione is a major factor contributing to the radioresistance observed in solid tumors. To address this radioresistance associated with glutathione, a cinnamaldehyde (CA) polymer prodrug, referred to as PDPCA, is fabricated. This prodrug is created by synthesizing a pendent CA prodrug with acetal linkages in a hydrophobic block, forming a self-assembled into a core-shell nanoparticle in aqueous media. Additionally, it encapsulates all-trans retinoic acid (ATRA) for synchronous delivery, resulting in PDPCA@ATRA. The PDPCA@ATRA nanoparticles accumulate reactive oxygen species through both endogenous and exogenous pathways, enhancing ferroptosis by depleting glutathione. This approach demonstrates efficacy in overcoming tumor radioresistance in vivo and in vitro, promoting the ferroptosis, and enhancing the cytotoxic T lymphocyte (CTL) response for lung tumors to anti-PD-1 (αPD-1) immunotherapy. Furthermore, this study reveals that PDPCA@ATRA nanoparticles promote ferroptosis through the NRF2-GPX4 signaling pathway, suggesting the potential for further investigation into the combination of radiotherapy and αPD-1 immune checkpoint inhibitors in cancer treatment.
Topics: Humans; Ferroptosis; Nanomedicine; Immunotherapy; Lung Neoplasms; Glutathione; Prodrugs; Reactive Oxygen Species; Cell Line, Tumor; Acrolein
PubMed: 38245863
DOI: 10.1002/adhm.202303412 -
Endocrine Connections Nov 2023Acrolein, an unsaturated aldehyde, plays a pathological role in neurodegenerative diseases. However, less is known about its effects on peripheral neuropathy. The aim of...
Acrolein, an unsaturated aldehyde, plays a pathological role in neurodegenerative diseases. However, less is known about its effects on peripheral neuropathy. The aim of this study was to investigate the association of acrolein and diabetic peripheral neuropathy in patients with type 2 diabetes. We recruited 148 ambulatory patients with type 2 diabetes. Each participant underwent an assessment of the Michigan Neuropathy Screening Instrument Physical Examination. Diabetic peripheral neuropathy was defined as Michigan Neuropathy Screening Instrument Physical Examination score ≥ 2.5. Serum levels and urinary levels of acrolein protein conjugates were measured. Urinary acrolein protein conjugates-to-creatinine ratios were determined. Patients with diabetic peripheral neuropathy had significantly higher urinary acrolein protein conjugates-to-creatinine ratios than those without diabetic peripheral neuropathy (7.91, 95% CI: 5.96-10.50 vs 5.31, 95% CI: 4.21-6.68, P = 0.029). Logarithmic transformation of urinary acrolein protein conjugates-to-creatinine ratios was positively associated with diabetic peripheral neuropathy in univariate logistic analysis, and the association remained significant in multivariate analysis (OR = 2.45, 95% CI: 1.12-5.34, P = 0.025). In conclusion, urinary acrolein protein conjugates-to-creatinine ratio may act as a new biomarker for diabetic peripheral neuropathy in type 2 diabetes. The involvement of acrolein in the pathogenesis of diabetic peripheral neuropathy warrants further investigation.
PubMed: 37698127
DOI: 10.1530/EC-23-0253 -
Environmental Science and Pollution... Sep 2023Schoolchildren are sensitive to airborne aldehyde exposures. The knowledge regarding inhalation exposure to aldehydes and the factors influencing exposure in...
Schoolchildren are sensitive to airborne aldehyde exposures. The knowledge regarding inhalation exposure to aldehydes and the factors influencing exposure in schoolchildren is limited. This study aimed to assess the variability and potential health risks of exposure to aldehydes (including formaldehyde) in schoolchildren. The important factors affecting personal exposure to aldehydes were also explored. Forty schoolchildren were recruited from the urban and suburban areas of Taiwan for aldehyde samplings and questionnaire surveys. Personal and indoor home samples of aldehydes were collected simultaneously during warm and cold seasons. We also identified the potential variables associated with aldehyde exposure based on the participant's responses to the questionnaires using mixed-effects models. The dominant three abundant aldehydes identified in personal exposure samples were formaldehyde (geometric mean, GM = 12.2 µg/m), acetaldehyde (GM = 5.53 µg/m), and hexaldehyde (GM = 8.79 µg/m), accounting for approximately 80% of the total selected aldehydes. Higher personal exposure to aldehydes was observed during the warm season. Moreover, the within-subject variance was predominant, accounting for 66.6 to > 99.9% of the total variance in exposure. Schoolchildren had a high probability of overexposure to formaldehyde and acrolein, which resulted in an incremental lifetime cancer risk of 1.59 × 10 (95th percentile = 4.64 × 10). Season, location, household refurbishment, and indoor ventilation variables were significantly associated with personal exposure to aldehydes. The results can improve our understanding of aldehyde exposure among schoolchildren to propose mitigation strategies. These findings may be applied to further epidemiological studies.
Topics: Humans; Child; Air Pollutants; Air Pollution, Indoor; Aldehydes; Formaldehyde; Surveys and Questionnaires
PubMed: 37653197
DOI: 10.1007/s11356-023-29578-3 -
BMC Public Health Sep 2023Glycerol, flavorings and sweeteners constitute approximately 70% of water-pipe tobacco smoking (WTS) mixtures. Tobacco mixture combustion produces smoke toxins (e.g....
Glycerol, flavorings and sweeteners constitute approximately 70% of water-pipe tobacco smoking (WTS) mixtures. Tobacco mixture combustion produces smoke toxins (e.g. carbonyl compounds), of which the type and amount are highly dependable on tobacco mixture formula. While glycerol in tobacco mixture contribute to enhanced smoking experience, its' combustion produces toxicants such as acrolein. According to WHO, there are no approved international upper limits regulations on WTS ingredients. This study aims to assess toxicant emission levels corresponding to increasing glycerol concentration in WTS mixtures, which may aid in developing tobacco regulations towards harm reduction.MethodsLaboratory experimental study. Using laboratory water-pipe smoking machine, levels of toxicant emissions in the smoke from WTS mixture samples containing varying glycerol concentrations were measured using High-performance Liquid Chromatography (HPLC). Smoke from 5 consecutive smoking cycles with 35 puffs each (ISO 22486 standard) was led through a trapping system as described in the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) recommended method No. 74 (Determination of selected carbonyls in mainstream cigarette smoke by HPLC). Trapped carbonyls were then analysed by HPLC with a DAD detector.ResultsAcrolein emission is associated with glycerol addition in WTS mixture indicated by lab-made samples throughout all glycerol concentrations (10%, 20%, 40% and 60%), and brand samples with glycerol concentrations 10% to 20%. However, brand samples showed no increase in acrolein emission corresponding to the increase in glycerol concentrations from 20% to 60%.ConclusionThe effect of glycerol addition in waterpipe tobacco on acrolein emission varies between products. Tobacco fillers, additives and contents quality and other factors may affect toxicant emission levels. Therefore, regulatory recommendations towards defining upper limits of content concentrations require further investigations regarding potential confounders in acrolein emissions and health effects of market-available glycerol concentrations in waterpipe tobacco smoking.
Topics: Humans; Tobacco, Waterpipe; Glycerol; Acrolein; Hazardous Substances; Tobacco Smoking
PubMed: 37749520
DOI: 10.1186/s12889-023-16740-2 -
The Journal of Physical Chemistry... Oct 2023This study reports the observation and characterization of two isomers of the acrolein dimer by using high-resolution rotational spectroscopy in pulsed jets. The first...
This study reports the observation and characterization of two isomers of the acrolein dimer by using high-resolution rotational spectroscopy in pulsed jets. The first isomer is stabilized by two hydrogen bonds, adopting a planar configuration, and is energetically favored over the second isomer, which exhibits a dominant n → π* interaction in a nearly orthogonal arrangement. Surprisingly, the n → π* interaction was revealed to enable a concerted tunneling motion of two moieties along the carbonyl group. This motion leads to the inversion of transient chirality associated with the exchange of donor-acceptor roles, as revealed by the spectral feature of quadruplets. Inversion of transient chirality is a fundamental phenomenon in quantum mechanics and commonly observed for only inversional motions of protons. It is the first discovery, to the best of our knowledge, that such heavy moieties can also undergo chirality inversion.
PubMed: 37756497
DOI: 10.1021/acs.jpclett.3c02264