-
Current Medical Science Aug 2023This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury (SCI) in the central nervous system (CNS) and its mechanism in...
OBJECTIVE
This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury (SCI) in the central nervous system (CNS) and its mechanism in promoting the structural and functional recovery of the injured CNS.
METHODS
A compressive SCI mouse model was utilized for this investigation. Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein, acrolein-induced inflammation-related factors, and macrophages at the injury site and within the CNS. Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase (PI3K)/AKT pathway to study macrophage regulation. The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67 (GAD65/67), vesicular glutamate transporter 1 (VGLUT1), paw withdrawal response, and Basso Mouse Scale score. Nissl staining and Luxol Fast Blue (LFB) staining were performed to investigate the structural recovery of the injured CNS.
RESULTS
Hydralazine downregulated the levels of acrolein, IL-1β, and TNF-α in the spinal cord. The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway, leading to M2 macrophage polarization, which protected neurons against SCI-induced inflammation. Additionally, hydralazine promoted the structural recovery of the injured spinal cord area. Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression. Furthermore, hydralazine facilitated motor function recovery following SCI. Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS.
CONCLUSION
Hydralazine, an acrolein scavenger, significantly mitigated SCI-induced inflammation and oxidative stress in vivo, modulated macrophage activation, and consequently promoted the structural and functional recovery of the injured CNS.
Topics: Rats; Mice; Animals; Phosphatidylinositol 3-Kinases; Acrolein; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Spinal Cord Injuries; Hydralazine; Neuralgia; Inflammation; Oxidative Stress; Macrophages
PubMed: 37558864
DOI: 10.1007/s11596-023-2767-9 -
Journal of Food Science Mar 2022Due to hydrophobicity, plant essential oil components trans-cinnamaldehyde and thymol exert broad-spectrum antimicrobial activities by interfering with the structures...
Due to hydrophobicity, plant essential oil components trans-cinnamaldehyde and thymol exert broad-spectrum antimicrobial activities by interfering with the structures and functions of microbial cell membranes, yet their antifungal properties against food-spoilage yeast Zygosaccharomyces rouxii are still unclear. This work aimed to elucidate their antifungal activities and mechanisms against Z. rouxii. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were measured using broth dilution method to evaluate the antifungal activities. Membrane permeability, potential and integrity, intracellular ATP content, and intracellular pH (pH ) were determined, and membrane damage was observed by scanning electron microscope (SEM) to investigate the antifungal mechanisms. The MICs of trans-cinnamaldehyde and thymol were 0.3125 and 0.0625 mg/ml, respectively, and the MFCs were 1.25 and 0.125 mg/ml, respectively. Increased membrane permeability, membrane hyperpolarization, decreased membrane integrity, reduced intracellular ATP content, and lowered pH were found after trans-cinnamaldehyde or thymol treatment at the MIC and MFC levels, and thymol exhibited more severe influence on cell membrane. SEM observation further confirmed that trans-cinnamaldehyde caused cell membrane shrinkage and invagination, while thymol resulted in perforation in cell membrane. These results suggest that trans-cinnamaldehyde and thymol exert anti-Z. rouxii activities by inducing cell membrane damage and subsequent intracellular homeostasis disruption. Cellular contents leakage and intracellular homeostasis disruption probably proceed more rapidly after thymol inducing perforation in the cell surface, thereby thymol exerting better anti-Z. rouxii activity. PRACTICAL APPLICATION: The addition of a small amount of thymol (0.125 mg/ml) is sufficient to effectively inhibit the growth of Z. rouxii in apple juice concentrate. Based on our previous work, the addition of thymol (0.125 mg/ml) in apple juice concentrate did not significantly affect the organoleptic property of the diluted apple juice (5°Brix) used for producing commercial apple juice products. Therefore, thymol is practical for application at the effective concentration (0.125 mg/ml) in apple juice concentrate.
Topics: Acrolein; Antifungal Agents; Saccharomyces cerevisiae; Saccharomycetales; Thymol; Zygosaccharomyces
PubMed: 35152410
DOI: 10.1111/1750-3841.16075 -
The Journal of Biological Chemistry 2021Natural antibodies, predominantly immunoglobulin M (IgM), play an important role in the defense against pathogens and in maintaining homeostasis against oxidized...
Natural antibodies, predominantly immunoglobulin M (IgM), play an important role in the defense against pathogens and in maintaining homeostasis against oxidized molecules known as oxidation-specific epitopes, such as those contained in oxidized low-density lipoproteins. However, owing to the complexity of the oxidized products, very few individual epitopes have been characterized in detail. In the present study, to identify endogenous sources of oxidation-specific epitopes, we stimulated mouse spleen and peritoneal cavity (PerC) cells in vitro with bovine serum albumin modified with a variety of lipid peroxidation-related carbonyl compounds and identified the acrolein-modified bovine serum albumin as the most efficient trigger studied for the production of IgM in PerC cells. The acrolein-specific epitopes accelerated the differentiation of B-1a cells, a fetal-derived B cell lineage, to plasma cells. In addition, acrolein-modified bovine serum albumin was specifically bound to B-1a cells, suggesting the presence of an acrolein-specific IgM-B cell receptor (BCR). A hybridoma, RE-G25, producing an acrolein-specific IgM, was established from the PerC cells and was indeed identified as a population of B cells expressing a specific IgM-BCR. In addition, we analyzed the BCR repertoire of acrolein-specific B cells and identified the most frequent IgM heavy chain gene segments of the B cells. These data established the presence of innate B cells expressing the acrolein-specific BCR and suggested that in addition to our understanding of acrolein as a toxic aldehyde, it may play a role as a trigger of the innate immune response.
Topics: Acrolein; Animals; Epitopes; Immunity, Innate; Immunoglobulin M; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Oxidation-Reduction; Receptors, Antigen, B-Cell
PubMed: 33839149
DOI: 10.1016/j.jbc.2021.100648 -
Journal of Hazardous Materials Apr 2020Acrolein (ACR) is a toxic contaminant for humans. Our previous research indicated that l-cysteine (Cys) decreased the cytotoxicity of acrolein possibly via adduct...
Acrolein (ACR) is a toxic contaminant for humans. Our previous research indicated that l-cysteine (Cys) decreased the cytotoxicity of acrolein possibly via adduct formation, but which adduct contributed to the toxicity-lowering effect remains unknown. In this work, we identified a di-cysteine acrolein adduct (ACR-di-Cys) and investigated its toxicity against human bronchial epithelial cell line HBE and colon cancer cell line Caco-2. ACR-di-Cys tremendously decreased acrolein-induced cytotoxicity via alleviating ROS and apoptosis intervention. In the condition of no presence of free cysteine, however, this adduct can convert to mono-ACR-Cys in PBS solution by losing a molecule of cysteine conjugated at CC bond. ACR-mono-Cys showed much higher toxicity than ACR-di-Cys, and even higher than acrolein after 48 h exposure. This study indicated that cysteine can react with acrolein to form adducts with different acrolein-detoxifying capacity, and a sufficient intake of cysteine or cysteine-containing proteins can maximize the detoxifying effect for acrolein via the formation of a highly detoxifying agent, ACR-di-Cys.
Topics: Acrolein; Apoptosis; Caco-2 Cells; Cell Survival; Cysteine; Humans; Reactive Oxygen Species
PubMed: 31780296
DOI: 10.1016/j.jhazmat.2019.121686 -
Toxicology and Industrial Health Nov 2023Smoking or occupational exposure leads to low concentrations of acrolein on the surface of the airways. Acrolein is involved in the pathophysiological processes of...
Smoking or occupational exposure leads to low concentrations of acrolein on the surface of the airways. Acrolein is involved in the pathophysiological processes of various respiratory diseases. Reports showed that acrolein induced an increase in mitochondrial reactive oxygen species (mROS). Furthermore, exogenous H₂O₂ was found to increase intracellular Zn⁺ concentration ([Zn⁺]ᵢ). However, the specific impact of acrolein on changes in intracellular Zn⁺ levels has not been fully investigated. Therefore, this study aimed to investigate the effects of acrolein on mROS and [Zn⁺]ᵢ in A549 cells. We used Mito Tracker Red CM-HXros (MitoROS) and Fluozin-3 fluorescent probes to observe changes in mROS and intracellular Zn⁺. The results revealed that acrolein increased [Zn⁺]ᵢ in a time- and dose-dependent manner. Additionally, the production of mROS was observed in response to acrolein treatment. Subsequent experiments showed that the intracellular Zn⁺ chelator TPEN could inhibit the acrolein-induced elevation of [Zn⁺]ᵢ but did not affect the acrolein-induced mROS production. Conversely, the acrolein-induced elevation of mROS and [Zn⁺]ᵢ were significantly decreased by the inhibitors of ROS formation (NaHSO₃, NAC). Furthermore, external oxygen free radicals increased both [Zn⁺]ᵢ levels and mROS production. These results demonstrated that acrolein-induced elevation of [Zn⁺]ᵢ in A549 cells was mediated by mROS generation, rather than through a pathway where [Zn⁺]ᵢ elevation leads to mROS production.
Topics: Humans; Reactive Oxygen Species; Oxidative Stress; Acrolein; A549 Cells; Hydrogen Peroxide; Zinc
PubMed: 37644888
DOI: 10.1177/07482337231198350 -
Journal of the Air & Waste Management... Dec 2020In the 2014 National Air Toxics Assessment (NATA), the carbonyl compounds formaldehyde and acetaldehyde were identified as key cancer risk drivers and acrolein was...
In the 2014 National Air Toxics Assessment (NATA), the carbonyl compounds formaldehyde and acetaldehyde were identified as key cancer risk drivers and acrolein was identified as one of the three air toxics that drive most of the noncancer risk. In this assessment, averaged across the Continental United States, about 75% of ambient formaldehyde and acetaldehyde, and about 18% of acrolein, is formed secondarily. This study was conducted to estimate the potential contribution to these secondarily formed carbonyl compounds from mobile sources. To develop such estimates, we conducted several CMAQ runs, where emissions are set to zero for different mobile source sectors, to determine their potential contribution. Although zeroing out emissions from an individual sector can offer only a rough approximation of how the sector might contribute to overall secondary concentrations, our results suggest that across the U. S., mobile sources contribute about 6-18% to secondary formaldehyde, 0-10% to secondary acetaldehyde, and 0-70% to secondary acrolein, depending on location. : Photochemical modeling of carbonyl compounds was conducted with emissions set to zero for various mobile source sectors to determine their contribution to secondary concentrations. Results indicated mobile sources contributed to total and secondary concentrations of formaldehyde, acetaldehyde, and acrolein in many locations across the U.S. with acrolein the dominant contributor in some locations. However, biogenic sources dominated secondary formaldehyde and acetaldehyde, and fires dominated secondary acrolein.
Topics: Acetaldehyde; Acrolein; Air Pollutants; Formaldehyde; Models, Theoretical; United States
PubMed: 32841108
DOI: 10.1080/10962247.2020.1813839 -
Journal of Alzheimer's Disease : JAD 2023Dementia, including Alzheimer's disease (AD), is one of the serious diseases at advanced age, and its early detection is important for maintaining quality of life (QOL).
BACKGROUND
Dementia, including Alzheimer's disease (AD), is one of the serious diseases at advanced age, and its early detection is important for maintaining quality of life (QOL).
OBJECTIVE
In this study, we sought novel biomarkers for dementia in urine.
METHODS
Samples of urine were collected from 57 control subjects without dementia, 62 mild cognitive impairment (MCI) patients, and 42 AD patients. Mini-Mental State Examination (MMSE) was evaluated when subjects were examined by medical doctors. Urinary amino acid (lysine)-conjugated acrolein (AC-Acro) was measured using N ɛ-(3-formyl-3, 4-dehydropiperidine) lysine (FDP-Lys) ELISA kit, and taurine content was measured using a taurine assay kit. Values were normalized by creatinine content which was measured with the colorimetric assay kit.
RESULTS
We found that urinary amino acid (lysine)-conjugated acrolein (AC-Acro) and taurine negatively correlated with MMSE score and are significantly lower in dementia patients compared to the normal subjects. When AC-Acro and taurine were evaluated together with age using an artificial neural network model, median relative risk values for subjects with AD, subjects with mild cognitive impairment, and control subjects were 0.96, 0.53, and 0.06, respectively.
CONCLUSION
Since urine is relatively easy to collect, our findings provide a novel biomarker for dementia without invasiveness.
Topics: Humans; Acrolein; Quality of Life; Lysine; Alzheimer Disease; Cognitive Dysfunction; Biomarkers
PubMed: 36744340
DOI: 10.3233/JAD-220912 -
Carcinogenesis Jun 2022DNA adducts are central in the mechanism of carcinogenesis by genotoxic agents. We compared levels of a DNA adduct of acrolein, a genotoxic carcinogen found in...
DNA adducts are central in the mechanism of carcinogenesis by genotoxic agents. We compared levels of a DNA adduct of acrolein, a genotoxic carcinogen found in e-cigarette vapor, in oral cell DNA of e-cigarette users and non-users of any tobacco or nicotine product. e-Cigarette users and non-users visited our clinic once monthly for 6 months, and oral brushings and urine samples were collected. For this study, we analyzed oral cell DNA adducts from three monthly visits in e-cigarette users and non-users as confirmed by urinary cyanoethyl mercapturic acid and total nicotine equivalents. DNA was isolated from the oral brushings and analyzed by a validated liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry method for the acrolein DNA adduct 8R/S-3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10-(3H)-one (γ-OH-Acr-dGuo). The median value of this DNA adduct in the e-cigarette users was 179 fmol/µmol dGuo (range 5.0 - 793 fmol/µmol dGuo) while that for non-users was 21.0 fmol/µmol dGuo (range 5.0 - 539 fmol/µmol dGuo), P = 0.001. These results demonstrate for the first time that e-cigarette users have elevated levels of a carcinogen-DNA adduct in their oral cells.
Topics: Acrolein; Carcinogens; Chromatography, High Pressure Liquid; DNA; DNA Adducts; Electronic Nicotine Delivery Systems; Nicotine; Spectrometry, Mass, Electrospray Ionization
PubMed: 35239969
DOI: 10.1093/carcin/bgac026 -
Toxicology and Applied Pharmacology Sep 2021Acrolein, an electrophilic α,β-unsaturated aldehyde, is present in foods and beverages, and is a product of incomplete combustion, and thus, reaches high ppm levels in...
Acrolein but not its metabolite, 3-Hydroxypropylmercapturic acid (3HPMA), activates vascular transient receptor potential Ankyrin-1 (TRPA1): Physiological to toxicological implications.
Acrolein, an electrophilic α,β-unsaturated aldehyde, is present in foods and beverages, and is a product of incomplete combustion, and thus, reaches high ppm levels in tobacco smoke and structural fires. Exposure to acrolein is linked with cardiopulmonary toxicity and cardiovascular disease risk. The hypothesis of this study is the direct effects of acrolein in isolated murine blood vessels (aorta and superior mesenteric artery, SMA) are transient receptor potential ankyrin-1 (TRPA1) dependent. Using isometric myography, isolated aorta and SMA were exposed to increasing levels of acrolein. Acrolein inhibited phenylephrine (PE)-induced contractions (approximately 90%) in aorta and SMA of male and female mice in a concentration-dependent (0.01-100 μM) manner. The major metabolite of acrolein, 3-hydroxypropylmercapturic acid (3HPMA), also relaxed PE-precontracted SMA. As the SMA was 20× more sensitive to acrolein than aorta (SMA EC 0.8 ± 0.2 μM; aorta EC > 29.4 ± 4.4 μM), the mechanisms of acrolein-induced relaxation were studied in SMA. The potency of acrolein-induced relaxation was inhibited significantly by: 1) mechanically-impaired endothelium; 2) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME); 3) guanylyl cyclase (GC) inhibitor (ODQ); and, 4) a TRPA1 antagonist (A967079). TRPA1 positive immunofluorescence was present in the endothelium. Compared with other known TRPA1 agonists, including allyl isothiocyanate (AITC), cinnamaldehyde, crotonaldehyde, and formaldehyde, acrolein stimulated a more potent TRPA1-dependent relaxation. Acrolein, at high concentration [100 μM], induced tension oscillations (spasms) independent of TRPA1 in precontracted SMA but not in aorta. In conclusion, acrolein is vasorelaxant at low levels (physiological) yet vasotoxic at high levels (toxicological).
Topics: Acetylcysteine; Acrolein; Animals; Aorta, Thoracic; Female; GTPase-Activating Proteins; Glutathione S-Transferase pi; Male; Mesenteric Artery, Superior; Mice, Inbred C57BL; Mice, Knockout; TRPA1 Cation Channel; Mice
PubMed: 34271065
DOI: 10.1016/j.taap.2021.115647 -
Journal of Food Science Apr 2023Acrolein is a toxic aldehyde that can be present in various beverages, such as cachaça and other distilled spirits from sugarcane. The objective of this work was to...
Acrolein is a toxic aldehyde that can be present in various beverages, such as cachaça and other distilled spirits from sugarcane. The objective of this work was to detect and quantify acrolein in samples of cachaça produced by different processes in all regions of Brazil and to evaluate the possible routes of formation of this contaminant from the correlation with other secondary compounds present in the beverage using principal component analysis. Approximately 27.0% of the samples analyzed were outside the limit established by Brazilian legislation for this contaminant, with an average acrolein concentration of 14.01 mg 100 mL anhydrous alcohol (aa). In the other samples, the average concentration was 0.97 mg 100 mL aa. After selecting the variables that most closely correlated with the presence of acrolein in beverages, a positive correlation was found with the presence of butan-2-ol, propan-1-ol and volatile acids, and a slight correlation with the presence of phenolic compounds. Therefore, the presence of acrolein in cachaça can be associated with contamination of the fermentation must by bacteria of the genus Lactobacillus, as a result of the chemical degradation and enzymatic conversion of the glycerol produced during fermentation.
Topics: Glycerol; Acrolein; Alcoholic Beverages; Beverages; Fermentation; Ethanol
PubMed: 36915964
DOI: 10.1111/1750-3841.16523