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Archives of Toxicology Jan 2018Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case... (Review)
Review
Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state of the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario's and risk assessment, and (6) the possibilities of novel methodologies. In spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment.
Topics: Acrolein; Acrylamide; Animals; Biomarkers; Dietary Exposure; Food Contamination; Food Handling; Furans; Humans; Models, Biological; Risk Assessment; alpha-Chlorohydrin
PubMed: 29302712
DOI: 10.1007/s00204-017-2143-2 -
International Journal of Molecular... Sep 2023It is reported that retinal abnormities are related to Alzheimer's disease (AD) in patients and animal models. However, it is unclear whether the retinal abnormities...
It is reported that retinal abnormities are related to Alzheimer's disease (AD) in patients and animal models. However, it is unclear whether the retinal abnormities appear in the mouse model of sporadic Alzheimer's disease (sAD) induced by acrolein. We investigated the alterations of retinal function and structure, the levels of β-amyloid (Aβ) and phosphorylated Tau (p-Tau) in the retina, and the changes in the retinal vascular system in this mouse model. We demonstrated that the levels of Aβ and p-Tau were increased in the retinas of mice from the acrolein groups. Subsequently, a decreased amplitudes of b-waves in the scotopic and photopic electroretinogram (ERG), decreased thicknesses of the retinal nerve fiber layer (RNFL) in the retina, and slight retinal venous beading were found in the mice induced by acrolein. We propose that sAD mice induced by acrolein showed abnormalities in the retina, which may provide a valuable reference for the study of the retina in sAD.
Topics: Animals; Mice; Alzheimer Disease; Acrolein; Retina; Amyloid beta-Peptides; Disease Models, Animal
PubMed: 37686379
DOI: 10.3390/ijms241713576 -
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 -
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 -
Yakugaku Zasshi : Journal of the... 2017Acrolein, a highly toxic α, β-unsaturated aldehyde, occurs as pollutant in the environment (e.g., tobacco smoke and exhaust gas) and is ubiquitously generated in... (Review)
Review
Acrolein, a highly toxic α, β-unsaturated aldehyde, occurs as pollutant in the environment (e.g., tobacco smoke and exhaust gas) and is ubiquitously generated in biosystems (e.g., the lipid peroxidation process and metabolism of polyamine or amino acids). High accumulation of acrolein in biosystems is often linked pathologically with several oxidative stress-related diseases, including cancer and Alzheimer's disease. Accordingly, acrolein holds great potential as a key biomarker in oxidative stress-related diseases, and direct measurement of acrolein in biological samples is important to provide information for diagnostic and therapeutic purposes. Recently, we have serendipitously discovered the unrecognized reactivity of phenyl azide to acrolein. Phenyl azide can rapidly and selectively react with acrolein in a "click" manner to provide 4-formyl-1,2,3-triazoline through 1,3-dipolar cycloaddition. We have successfully utilized the acrolein-azide click reaction as a simple but robust method for detecting and visualizing acrolein generated by live cells in the context of oxidative stress processes. In addition, we also serendipitously discovered novel cycloaddition reactions of N-alkyl-α,β-unsaturated imines derived from acrolein and biogenic amines (e.g., polyamines, norepinephrine, and sphingosine), to yield 8-membered cyclic compounds. We then examined the biological functions of the cyclic products and revealed for the first time their roles in the oxidative stress mechanism and inhibition of amyloid β(1-40) fibrillization.
Topics: Acrolein; Alzheimer Disease; Amyloid beta-Peptides; Azides; Biogenic Amines; Biomarkers; Cycloaddition Reaction; Environmental Pollutants; Imines; Molecular Imaging; Neoplasms; Oxidative Stress; Peptide Fragments
PubMed: 28250324
DOI: 10.1248/yakushi.16-00231-3 -
The EMBO Journal Nov 2022Retrograde transport of lysosomes is recognised as a critical autophagy regulator. Here, we found that acrolein, an aldehyde that is significantly elevated in...
Retrograde transport of lysosomes is recognised as a critical autophagy regulator. Here, we found that acrolein, an aldehyde that is significantly elevated in Parkinson's disease patient serum, enhances autophagy by promoting lysosomal clustering around the microtubule organising centre via a newly identified JIP4-TRPML1-ALG2 pathway. Phosphorylation of JIP4 at T217 by CaMK2G in response to Ca fluxes tightly regulated this system. Increased vulnerability of JIP4 KO cells to acrolein indicated that lysosomal clustering and subsequent autophagy activation served as defence mechanisms against cytotoxicity of acrolein itself. Furthermore, the JIP4-TRPML1-ALG2 pathway was also activated by H O , indicating that this system acts as a broad mechanism of the oxidative stress response. Conversely, starvation-induced lysosomal retrograde transport involved both the TMEM55B-JIP4 and TRPML1-ALG2 pathways in the absence of the JIP4 phosphorylation. Therefore, the phosphorylation status of JIP4 acts as a switch that controls the signalling pathways of lysosoma l distribution depending on the type of autophagy-inducing signal.
Topics: Humans; Acrolein; Transient Receptor Potential Channels; Lysosomes; Oxidative Phosphorylation; Oxidative Stress
PubMed: 36394115
DOI: 10.15252/embj.2022111476 -
Oncotarget Jun 2014Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants,...
Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.
Topics: Acrolein; Aminobiphenyl Compounds; Cells, Cultured; DNA Adducts; DNA Repair; Humans; Mutagenesis; Urinary Bladder Neoplasms; Urothelium
PubMed: 24939871
DOI: 10.18632/oncotarget.1954 -
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 -
Molecular Nutrition & Food Research Sep 2011Acrolein (Acr) is a ubiquitous environmental contaminant; it also can be generated endogenously by lipid peroxidation. Acr contains a carbonyl group and an olefinic... (Review)
Review
Acrolein (Acr) is a ubiquitous environmental contaminant; it also can be generated endogenously by lipid peroxidation. Acr contains a carbonyl group and an olefinic double bond; it can react with many cellular molecules including amino acids, proteins and nucleic acids. In this review article we focus on updating information regarding: (i) Acr-induced DNA damage and methods of detection, (ii) repair of Acr-DNA damage, (iii) mutagenicity of Acr-DNA adducts, (iv) sequence specificity and methylation effect on Acr-DNA adduct formation and (v) the role of Acr in human cancer. We have found that Acr can inhibit DNA repair and induces mutagenic Acr-dG adducts and that the binding spectrum of Acr in the p53 gene in normal human bronchial epithelial cells is similar to the p53 mutational spectrum in lung cancer. Since Acr-DNA adduct has been identified in human lung tissue and Acr causes bladder cancer in human and rat models, we conclude that Acr is a major lung and bladder carcinogen, and its carcinogenicity arises via induction of DNA damage and inhibition of DNA repair.
Topics: Acrolein; Animals; Carcinogenicity Tests; Carcinogens; DNA Adducts; DNA Damage; DNA Repair; Humans; Lipid Peroxidation; Lung Neoplasms; Mutagenicity Tests; Mutation; Rats; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms
PubMed: 21714128
DOI: 10.1002/mnfr.201100148