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Expert Review of Neurotherapeutics Jun 2014Oxidative stress has been implicated as a major pathological process underlying CNS disease and trauma. More specifically, acrolein, an unsaturated aldehyde, produced by... (Review)
Review
Oxidative stress has been implicated as a major pathological process underlying CNS disease and trauma. More specifically, acrolein, an unsaturated aldehyde, produced by way of lipid peroxidation, has been shown to play a crucial role in initiating and perpetuating detrimental effects associated with multiple sclerosis and spinal cord injury. In light of these findings, quantification of acrolein levels both systemically and locally could allow for the use of acrolein as a biomarker to aid in diagnosis and guide treatment regimens. The three main approaches currently available are acrolein derivatization followed by LC/GC-MS, application of an acrolein antibody and subsequent immunoblotting, and the 3-hydroxypropylmercapturic acid-based method. Of these three strategies, the 3-hydroxypropylmercapturic acid-based method is the least invasive allowing for rapid translation of acrolein detection into a clinical setting.
Topics: Acrolein; Humans; Lipid Peroxidation; Multiple Sclerosis; Oxidative Stress; Spinal Cord Injuries
PubMed: 24831349
DOI: 10.1586/14737175.2014.918849 -
Nature Communications Oct 2022E-cigarette use has surged, but the long-term health effects remain unknown. E-cigarette aerosols containing nicotine and acrolein, a combustion and e-cigarette...
E-cigarette use has surged, but the long-term health effects remain unknown. E-cigarette aerosols containing nicotine and acrolein, a combustion and e-cigarette byproduct, may impair cardiac electrophysiology through autonomic imbalance. Here we show in mouse electrocardiograms that acute inhalation of e-cigarette aerosols disturbs cardiac conduction, in part through parasympathetic modulation. We demonstrate that, similar to acrolein or combustible cigarette smoke, aerosols from e-cigarette solvents (vegetable glycerin and propylene glycol) induce bradycardia, bradyarrhythmias, and elevations in heart rate variability during inhalation exposure, with inverse post-exposure effects. These effects are slighter with tobacco- or menthol-flavored aerosols containing nicotine, and in female mice. Yet, menthol-flavored and PG aerosols also increase ventricular arrhythmias and augment early ventricular repolarization (J amplitude), while menthol uniquely alters atrial and atrioventricular conduction. Exposure to e-cigarette aerosols from vegetable glycerin and its byproduct, acrolein, diminish heart rate and early repolarization. The pro-arrhythmic effects of solvent aerosols on ventricular repolarization and heart rate variability depend partly on parasympathetic modulation, whereas ventricular arrhythmias positively associate with early repolarization dependent on the presence of nicotine. Our study indicates that chemical constituents of e-cigarettes could contribute to cardiac risk by provoking pro-arrhythmic changes and stimulating autonomic reflexes.
Topics: Animals; Female; Mice; Acrolein; Aerosols; Arrhythmias, Cardiac; Electronic Nicotine Delivery Systems; Glycerol; Menthol; Nicotine; Propylene Glycol; Solvents; Nicotiana; Vegetables
PubMed: 36284091
DOI: 10.1038/s41467-022-33203-1 -
Chemical Research in Toxicology Feb 2022Despite the increasing popularity of e-cigarettes, their long-term health effects remain unknown. In animal models, exposure to e-cigarette has been reported to result...
Despite the increasing popularity of e-cigarettes, their long-term health effects remain unknown. In animal models, exposure to e-cigarette has been reported to result in pulmonary and cardiovascular injury, and in humans, the acute use of e-cigarettes increases heart rate and blood pressure and induces endothelial dysfunction. In both animal models and humans, cardiovascular dysfunction associated with e-cigarettes has been linked to reactive aldehydes such as formaldehyde and acrolein generated in e-cigarette aerosols. These aldehydes are known products of heating and degradation of vegetable glycerin (VG) present in e-liquids. Here, we report that in mice, acute exposure to a mixture of propylene glycol:vegetable glycerin (PG:VG) or to e-cigarette-derived aerosols significantly increased the urinary excretion of acrolein and glycidol metabolites─3-hydroxypropylmercapturic acid (3HPMA) and 2,3-dihydroxypropylmercapturic acid (23HPMA)─as measured by UPLC-MS/MS. In humans, the use of e-cigarettes led to an increase in the urinary levels of 23HPMA but not 3HPMA. Acute exposure of mice to aerosols derived from PG:C-VG significantly increased the C enrichment of both urinary metabolites C-3HPMA and C-23HPMA. Our stable isotope tracing experiments provide further evidence that thermal decomposition of vegetable glycerin in the e-cigarette solvent leads to generation of acrolein and glycidol. This suggests that the adverse health effects of e-cigarettes may be attributable in part to these reactive compounds formed through the process of aerosolizing nicotine. Our findings also support the notion that 23HPMA, but not 3HPMA, may be a relatively specific biomarker of e-cigarette use.
Topics: Acrolein; Aerosols; Animals; Biomarkers; Chromatography, High Pressure Liquid; Electronic Nicotine Delivery Systems; Epoxy Compounds; Flavoring Agents; Male; Mass Spectrometry; Mice; Mice, Inbred C57BL; Propanols; Solvents; Vaping
PubMed: 35044764
DOI: 10.1021/acs.chemrestox.1c00328 -
Food Chemistry Aug 2022A new, fast, simple, and effective ultrasound-assisted dispersive liquid-liquid microextraction procedure (UA-DLLME) for the gas chromatography-mass spectrometry (GC-MS)...
A new, fast, simple, and effective ultrasound-assisted dispersive liquid-liquid microextraction procedure (UA-DLLME) for the gas chromatography-mass spectrometry (GC-MS) determination of malondialdehyde, acrolein, and 4-hydroxy-2-nonenal in beverages was successfully developed. 2,4-Dinitrophenylhydrazine derivatization was performed during extraction. An asymmetrical 34//18 screening design and a central composite surface response design were used to investigate the influence of the most critical factors during the extraction process (ultrasound time and temperature, extraction and disperser solvents volumes, salt addition, and derivatization reagent concentration). According to FDA guidelines, the method was validated, achieving good linearities with r ≥ 0.9982, recoveries between 94.0 and 102.4%, and reproducibility with RSD lower than 4.5%. The method was applied to simultaneously determine the compounds in 60 different beverage samples, including beer, coffee, black tea, and fruit juices. The presence of secondary lipid oxidation products is demonstrated in beverages with a strong roasting process or oxidation.
Topics: Acrolein; Aldehydes; Beverages; Gas Chromatography-Mass Spectrometry; Limit of Detection; Liquid Phase Microextraction; Malondialdehyde; Reproducibility of Results
PubMed: 35227997
DOI: 10.1016/j.foodchem.2022.132530 -
Toxicology Mar 2022Exposure of the airways to cigarette smoke (CS) is the primary risk factor for developing several lung diseases such as Chronic Obstructive Pulmonary Disease (COPD). CS...
Exposure of the airways to cigarette smoke (CS) is the primary risk factor for developing several lung diseases such as Chronic Obstructive Pulmonary Disease (COPD). CS consists of a complex mixture of over 6000 chemicals including the highly reactive α,β-unsaturated aldehyde acrolein. Acrolein is thought to be responsible for a large proportion of the non-cancer disease risk associated with smoking. Emerging evidence suggest a key role for CS-induced abnormalities in mitochondrial morphology and function in airway epithelial cells in COPD pathogenesis. Although in vitro studies suggest acrolein-induced mitochondrial dysfunction in airway epithelial cells, it is unknown if in vivo inhalation of acrolein affects mitochondrial content or the pathways controlling this. In this study, rats were acutely exposed to acrolein by inhalation (nose-only; 0-4 ppm), 4 h/day for 1 or 2 consecutive days (n = 6/group). Subsequently, the activity and abundance of key constituents of mitochondrial metabolic pathways as well as expression of critical proteins and genes controlling mitochondrial biogenesis and mitophagy were investigated in lung homogenates. A transient decreasing response in protein and transcript abundance of subunits of the electron transport chain complexes was observed following acrolein inhalation. Moreover, acrolein inhalation caused a decreased abundance of key regulators associated with mitochondrial biogenesis, respectively a differential response on day 1 versus day 2. Abundance of components of the mitophagy machinery was in general unaltered in response to acrolein exposure in rat lung. Collectively, this study demonstrates that acrolein inhalation acutely and dose-dependently disrupts the molecular regulation of mitochondrial metabolism in rat lung. Hence, understanding the effect of acrolein on mitochondrial function will provide a scientifically supported reasoning to shortlist aldehydes regulation in tobacco smoke.
Topics: Acrolein; Administration, Inhalation; Aldehydes; Animals; Lung; Mitochondria; Pulmonary Disease, Chronic Obstructive; Rats; Nicotiana
PubMed: 35150775
DOI: 10.1016/j.tox.2022.153129 -
Journal of Neurochemistry Dec 2009It has long been established that oxidative stress plays a critical role in the pathophysiology of spinal cord injury, and represents an important target of therapeutic... (Review)
Review
It has long been established that oxidative stress plays a critical role in the pathophysiology of spinal cord injury, and represents an important target of therapeutic intervention following the initial trauma. However, free radical scavengers have been largely ineffective in clinical trials, and as such a novel target to attenuate oxidative stress is highly warranted. In addition to free radicals, peroxidation of lipid membranes following spinal cord injury (SCI) produces reactive aldehydes such as acrolein. Acrolein is capable of depleting endogenous antioxidants such as glutathione, generating free radicals, promoting oxidative stress, and damaging proteins and DNA. Acrolein has a significantly longer half-life than the transient free radicals, and thus may represent a potentially better target of therapeutic intervention to attenuate oxidative stress. There is growing evidence, from our lab and others, to suggest that reactive aldehydes such as acrolein play a critical role in oxidative stress and SCI. The focus of this review is to summarize the cellular and biochemical mechanisms of acrolein-induced membrane damage, mitochondrial injury, oxidative stress, cell death, and functional loss. Evidence will also be presented to suggest that acrolein scavenging may be a novel means of therapeutic intervention to attenuate oxidative stress and improve recovery following traumatic SCI.
Topics: Acrolein; Animals; Free Radical Scavengers; Humans; Hydralazine; Lipid Peroxidation; Models, Biological; Oxidative Stress; Spinal Cord Injuries
PubMed: 19780896
DOI: 10.1111/j.1471-4159.2009.06395.x -
Journal of Applied Microbiology Feb 2022In the context of minor orthodontic intervention using clear aligner technologies, we determined antimicrobial properties of a cellulose-based material loaded with...
AIMS
In the context of minor orthodontic intervention using clear aligner technologies, we determined antimicrobial properties of a cellulose-based material loaded with essential oils such as cinnamaldehyde.
METHODS AND RESULTS
Isothermal microcalorimetry was used to assess the growth of bacterial biofilms at the interface between the tested material and the solid growth medium. The calorimetric data were analyzed using conventional growth models (Gompertz and Richards), and inhibition at 12 and 24 h was calculated.
CONCLUSIONS
The tested material showed antimicrobial properties against Staphylococcus epidermidis as well as Streptococcus mutans and Streptococcus mitis clinical isolates. The inhibition was more pronounced against S. epidermidis, for which growth rate was reduced by 70% and lag phase was extended by 12 h. For S. mutans and S. mitis, the decrease in growth rate was 20% and 10%, and the lag phase increased by 2 and 6 h, respectively.
SIGNIFICANCE AND IMPACT
Clear aligners for minor teeth alignment are becoming very popular. As they must be worn for at least 22 h per day for up to 40 weeks, it is important that they remain clean and do not promote caries formation or other oral infections. Therefore, introducing material with antimicrobial properties is expected to maintain oral hygiene during the aligner therapy. Here, we demonstrate the use of cinnamaldehyde for reducing microbial growth and biofilm formation on cellulose-based dental clear aligners.
Topics: Acrolein; Anti-Infective Agents; Biofilms; Cellulose; Dental Caries; Humans; Streptococcus mutans
PubMed: 34480822
DOI: 10.1111/jam.15283 -
Journal of Toxicology and Environmental... 2015The Texas Commission on Environmental Quality (TCEQ) conducted a chronic inhalation noncancer toxicity assessment for crotonaldehyde (CRO). Since there were limited... (Review)
Review
The Texas Commission on Environmental Quality (TCEQ) conducted a chronic inhalation noncancer toxicity assessment for crotonaldehyde (CRO). Since there were limited toxicity data for CRO, a reference value (ReV) was derived using a relative potency factor (RPF) approach with acrolein as the index chemical. Both CRO and acrolein are α,β-unsaturated carbonyls and share common steps in their mode of action (MOA). Only studies that investigated the effects of CRO and acrolein in the same study were used to calculate a CRO:acrolein RPF. In vivo findings measuring both 50% respiratory depression in rats and two species of mice and subcutaneous 50% lethality in rats and mice were used to calculate an RPF of 3 (rounded to one significant figure). In vitro data were useful to compare the MOA of CRO and acrolein and to support the RPF determined using in vivo data. In vitro cell culture studies investigating cytotoxicity in normal human lung fibroblast cultures using the propidium iodide cytotoxicity assay and in mouse lymphocyte cultures using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay were used to calculate an in vitro RPF of 3, which supports the in vivo RPF. The chronic ReV for acrolein of 1.2 ppb derived by TCEQ was multiplied by the RPF of 3 to calculate the ReV for CRO of 3.6 ppb (10 μg/m(3)). The ReV for CRO was developed to protect the general public from adverse health effects from chronic exposure to CRO in ambient air.
Topics: Acrolein; Aldehydes; Animals; Environmental Pollutants; Humans; Mice; Rats; Reference Values; Risk Assessment
PubMed: 26580244
DOI: 10.1080/10937404.2015.1081574 -
BioMed Research International 2020Neurodegenerative diseases are devastating and incurable disorders characterized by neuronal dysfunction. The major focus of experimental and clinical studies are... (Review)
Review
Neurodegenerative diseases are devastating and incurable disorders characterized by neuronal dysfunction. The major focus of experimental and clinical studies are conducted on the effects of natural products and their active components on neurodegenerative diseases. This review will discuss an herbal constituent known as cinnamaldehyde (CA) with the neuroprotective potential to treat neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Accumulating evidence supports the notion that CA displays neuroprotective effects in AD and PD animal models by modulating neuroinflammation, suppressing oxidative stress, and improving the synaptic connection. CA exerts these effects through its action on multiple signaling pathways, including TLR4/NF-B, NLRP3, ERK1/2-MEK, NO, and Nrf2 pathways. To summarize, CA and its derivatives have been shown to improve pathological changes in AD and PD animal models, which may provide a new therapeutic option for neurodegenerative interventions. To this end, further experimental and clinical studies are required to prove the neuroprotective effects of CA and its derivatives.
Topics: Acrolein; Animals; Disease Models, Animal; Disease Progression; Humans; Inflammation; Neurodegenerative Diseases; Neuroprotective Agents
PubMed: 33274192
DOI: 10.1155/2020/1034325 -
Environment International Oct 2020Aldehydes are common air pollutants with carcinogenicity. Genotoxicity of single aldehyde has been studied well, but the combined genotoxicity is rarely known. Here, we...
Aldehydes are common air pollutants with carcinogenicity. Genotoxicity of single aldehyde has been studied well, but the combined genotoxicity is rarely known. Here, we evaluated the combined genotoxicity of formaldehyde and acrolein on BEAS-2B cells in terms of DNA strands breakage, chromosome damage and gene mutation below subcytotoxic concentrations covering smoking-related concentrations. Meanwhile, the molecular mechanism was investigated further based on oxidative stress, DNA-protein crosslinks (DPCs), cell cycle and DNA damage-repair pathway. Co-exposure to formaldehyde and acrolein mixtures showed significantly synergistic interaction on DNA strands breakage and chromosome damage in a concentration/time-dependent manner, while antagonism was shown on the late genotoxic endpoints (e.g. cytoplasmic block micronucleus (CBMN) and HPRT gene mutation). Moreover, formaldehyde synergistically potentiated acrolein-induced S-phase arrest, inhibition of DNA repair and up-regulation of genes related to cell stress, which conversely strengtherned mixture-induced DNA/chromosome damage and finally resulted in antagonism on late genotoxic events. Additionally, formaldehyde-induced DNA damage mainly resulted from the direct covalent bonding (e.g. DPCs), while acrolein-induced DNA damage mainly generated from oxidative damage (e.g. oxidative stress), which dominated the synergistic DNA strand breakage induced by mixtures. Summarily, aldehyde mixtures (formaldehyde and acrolein) induced multiplex combined genotoxicity on BEAS-2B cells even at smoking-related concentrations, which was dependent on genotoxic endpoints and closely related to that formaldehyde potentiated acrolein-induced cell stress, S-phase arrest and inhibition of DNA repair. So prolonged exposure to aldehyde mixtures may have a more serious risk to respiratory system in animal and human than the expectation based on the toxicity of single aldehyde even at environmentally relevant concentrations.
Topics: Acrolein; Aldehydes; Animals; DNA Damage; Epithelial Cells; Formaldehyde; Humans
PubMed: 32659531
DOI: 10.1016/j.envint.2020.105943