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Environmental Toxicology and... Jul 2022Cardiovascular disease, the foremost cause of death worldwide, is an overarching disease term that encompasses a number of disorders involving the heart and circulatory... (Review)
Review
Cardiovascular disease, the foremost cause of death worldwide, is an overarching disease term that encompasses a number of disorders involving the heart and circulatory system, including atherosclerosis. Atherosclerosis is a primary cause of cardiovascular diseases and is caused by buildup of plaque and narrowing of blood vessels. Epidemiological studies have suggested that environmental pollutants are implicated in atherosclerosis disease progression. Among many environmental pollutants, acrolein (Acr) is an abundant reactive aldehyde and is ubiquitously present in cigarette smoke as well as food products (e.g., overheated oils and wine). Despite its ubiquitous presence and potential impact on the etiology of cardiovascular disease, a limited consensus has been made in regard to Acr exposure conditions to induce atherosclerosis in vivo. This mini-review summarizes in vivo atherosclerosis models using Acr to investigate biochemical and phenotypic changes related to atherosclerosis and in vitro mechanistic studies involving Acr and atherosclerosis.
Topics: Acrolein; Aldehydes; Atherosclerosis; Cardiovascular Diseases; Environmental Pollutants; Hazardous Substances; Humans
PubMed: 35613694
DOI: 10.1016/j.etap.2022.103890 -
Chemical Research in Toxicology Jul 2020Albumin is an abundant protein in the lung lining fluid that forms an interface between lung epithelial cells and the external environment. In the lung, albumin can be...
Albumin is an abundant protein in the lung lining fluid that forms an interface between lung epithelial cells and the external environment. In the lung, albumin can be targeted for adduction by inhaled acrolein. Acrolein, an α,β-unsaturated aldehyde, reacts with biomolecules via Michael addition at the β-carbon or Schiff base formation at the carbonyl carbon. To gain insight into acrolein's mode of action, we investigated albumin-acrolein reactivity and the consequence of albumin adduction by acrolein on cytotoxicity and transcript changes in NCI-H441 and human airway epithelial cells (HAEC). Albumin protected NCI-H441 cells from acrolein toxicity. In addition, albumin inhibited acrolein-induced increase of transcripts associated with cellular stress response, activating transcription factor 3 (ATF3), and antioxidant response, heme oxygenase 1 (HMOX1) in HAEC cells. Acrolein-adducted albumin itself increased HMOX1 transcripts but not ATF3 transcripts. The HMOX1 transcript increase was inhibited by hydralazine, a carbonyl scavenger, suggesting that the carbonyl group of acrolein-adducted albumin mediated HMOX1 transcript increase. In acutely exposed C57BL/6J mice, bronchoalveolar lavage protein carbonylation increased. Acrolein-adducted albumin Cys34 was identified by nLC-MS/MS. These findings indicate that adduction of albumin by acrolein confers a cytoprotective function by scavenging free acrolein, decreasing a cellular stress response, and inducing an antioxidant gene response. Further, these results suggest that β-carbon reactivity may be required for acrolein's cytotoxicity and ATF3 transcript increase, and the carbonyl group of acrolein-adducted albumin can induce HMOX1 transcript increase.
Topics: Acrolein; Activating Transcription Factor 3; Albumins; Animals; Bronchoalveolar Lavage Fluid; Cells, Cultured; Heme Oxygenase-1; Humans; Lung; Mice, Inbred C57BL; Protein Binding; Protein Carbonylation; Transcription, Genetic
PubMed: 32530271
DOI: 10.1021/acs.chemrestox.0c00146 -
Toxicology and Industrial Health Feb 2020In this study, the effects of a potent antioxidant, selenium, on apoptosis induced by acrolein, a cytotoxic and genotoxic environmental pollutant, were investigated by... (Comparative Study)
Comparative Study
In this study, the effects of a potent antioxidant, selenium, on apoptosis induced by acrolein, a cytotoxic and genotoxic environmental pollutant, were investigated by immunohistochemical and electron microscopic methods. One hundred adult male Wistar albino rats were used in the study. The rats were divided into four main groups: control, acrolein, selenium, and acrolein + selenium. The animals in the experimental groups were given 1 mg/kg/day selenium and 4 mg/kg/day acrolein daily for 7 days by gavage. After drug administration, each group was divided into subgroups according to the time they were to be euthanized: 12th hour, 1st, 2nd, 3rd, and 5th day. The rats in each group at the determined time were euthanized and their livers were removed. Routine histological procedures were performed for light and electron microscopy examinations. After applying the Terminal Deoxynucleotidyl Transferase dUTP nick end labeling assay on the liver sections, apoptotic index values were calculated. Comparing the liver sections of the rats in the acrolein group and the control group, acrolein was found to cause a significant increase in the apoptotic index. The apoptotic index values of the acrolein + selenium group decreased compared to the acrolein group. In the electron microscopic examinations, apoptotic findings were observed in the liver tissues of the rats given acrolein, such as chromatin condensation in the nucleus of hepatocytes, dilatations in the perinuclear space, and cytoplasmic vacuolization. These apoptotic findings were not observed in the acrolein + selenium group after the 12th hour. These findings show that selenium may potentially be useful as a protective agent for people exposed to acrolein.
Topics: Acrolein; Animals; Antioxidants; Apoptosis; Euthanasia, Animal; Liver; Male; Rats; Rats, Wistar; Selenium
PubMed: 32279646
DOI: 10.1177/0748233720909043 -
Bioorganic & Medicinal Chemistry Dec 2020Acrolein, a highly reactive α,β-unsaturated aldehyde, is a compound to which humans are exposed in many different situations and often causes various human diseases.... (Review)
Review
Acrolein, a highly reactive α,β-unsaturated aldehyde, is a compound to which humans are exposed in many different situations and often causes various human diseases. This paper summarizes the reports over the past twenty-five years regarding disease-associated acrolein detected in clinical patients and the role acrolein plays in various diseases. In several diseases, it was found that the increased acrolein acts as a pathogenetic factor. Thus, we propose the utility of over-produced acrolein as a substrate for a promising therapeutic or diagnostic method applicable to a wide range of diseases based on an in vivo synthetic chemistry strategy.
Topics: Acrolein; Alzheimer Disease; Autoimmune Diseases; Brain Diseases; Humans; Lysine; Polyamines; Proteins
PubMed: 33199202
DOI: 10.1016/j.bmc.2020.115831 -
Chemical Record (New York, N.Y.) Apr 2021N-alkyl unsaturated imines derived from acrolein, a toxin produced during oxidative stress, and biogenic alkyl amines occur naturally and are considered biologically... (Review)
Review
N-alkyl unsaturated imines derived from acrolein, a toxin produced during oxidative stress, and biogenic alkyl amines occur naturally and are considered biologically relevant compounds. However, despite the recent conceptual and technological advances in organic synthesis, research on the new reactivity of these compounds is lacking. This personal account discusses research on the reactivity that has been overlooked in acrolein imines, including the discovery of new methods to synthesize biologically active compounds, the determination of new functions of relevant imines and their precursors, i. e., aldehydes and amines, and the application of these methods for clinical diagnosis.
Topics: Acrolein; Alzheimer Disease; Breast Neoplasms; Female; Humans; Imines; Molecular Structure; Oxidative Stress
PubMed: 33769681
DOI: 10.1002/tcr.202000146 -
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 -
European Journal of Endocrinology Oct 2022Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a major chronic complication of diabetes and is the most frequent cause of kidney failure...
OBJECTIVE
Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a major chronic complication of diabetes and is the most frequent cause of kidney failure globally. A better understanding of the pathophysiology of DN would lead to the development of novel therapeutic options. Acrolein, an α,β-unsaturated aldehyde, is a common dietary and environmental pollutant.
DESIGN
The role of acrolein and the potential protective action of acrolein scavengers in DN were investigated using high-fat diet/ streptozotocin-induced DN mice and in vitro DN cellular models.
METHODS
Acrolein-protein conjugates (Acr-PCs) in kidney tissues were examined using immunohistochemistry. Renin-angiotensin system (RAS) and downstream signaling pathways were analyzed using quantitative RT-PCR and Western blot analyses. Acr-PCs in DN patients were analyzed using an established Acr-PC ELISA system.
RESULTS
We found an increase in Acr-PCs in kidney cells using in vivo and in vitro DN models. Hyperglycemia activated the RAS and downstream MAPK pathways, increasing inflammatory cytokines and cellular apoptosis in two human kidney cell lines (HK2 and HEK293). A similar effect was induced by acrolein. Furthermore, acrolein scavengers such as N-acetylcysteine, hydralazine, and carnosine could ameliorate diabetes-induced kidney injury. Clinically, we also found increased Acr-PCs in serum samples or kidney tissues of DKD patients compared to normal volunteers, and the Acr-PCs were negatively correlated with kidney function.
CONCLUSIONS
These results together suggest that acrolein plays a role in the pathogenesis of DN and could be a diagnostic marker and effective therapeutic target to ameliorate the development of DN.
Topics: Acetylcysteine; Acrolein; Animals; Carnosine; Cytokines; Diabetes Mellitus; Diabetic Nephropathies; Environmental Pollutants; HEK293 Cells; Humans; Hydralazine; Kidney; Mice; Streptozocin
PubMed: 36001357
DOI: 10.1530/EJE-22-0493 -
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 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 -
Scientific Reports Dec 2023Acrolein, a respiratory irritant, induces systemic neuroendocrine stress. However, peripheral metabolic effects have not been examined. Male and female WKY rats were...
Acrolein, a respiratory irritant, induces systemic neuroendocrine stress. However, peripheral metabolic effects have not been examined. Male and female WKY rats were exposed to air (0 ppm) or acrolein (3.16 ppm) for 4 h, followed by immediate serum and liver tissue collection. Serum metabolomics in both sexes and liver transcriptomics in males were evaluated to characterize the systemic metabolic response. Of 887 identified metabolites, > 400 differed between sexes at baseline. An acrolein biomarker, 3-hydroxypropyl mercapturic acid, increased 18-fold in males and 33-fold in females, indicating greater metabolic detoxification in females than males. Acrolein exposure changed 174 metabolites in males but only 50 in females. Metabolic process assessment identified higher circulating free-fatty acids, glycerols, and other lipids in male but not female rats exposed to acrolein. In males, acrolein also increased branched-chain amino acids, which was linked with metabolites of nitrogen imbalance within the gut microbiome. The contribution of neuroendocrine stress was evident by increased corticosterone in males but not females. Male liver transcriptomics revealed acrolein-induced over-representation of lipid and protein metabolic processes, and pathway alterations including Sirtuin, insulin-receptor, acute-phase, and glucocorticoid signaling. In sum, acute acrolein inhalation resulted in sex-specific serum metabolomic and liver transcriptomic derangement, which may have connections to chronic metabolic-related diseases.
Topics: Rats; Male; Female; Animals; Acrolein; Transcriptome; Rats, Inbred WKY; Liver; Metabolome
PubMed: 38040807
DOI: 10.1038/s41598-023-48413-w