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Critical Reviews in Toxicology Aug 2005Aldehydes are organic compounds that are widespread in nature. They can be formed endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate... (Review)
Review
Aldehydes are organic compounds that are widespread in nature. They can be formed endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate autoxidation, amine oxidases, cytochrome P-450s, or myeloperoxidase-catalyzed metabolic activation. This review compares the reactivity of many aldehydes towards biomolecules particularly macromolecules. Furthermore, it includes not only aldehydes of environmental or occupational concerns but also dietary aldehydes and aldehydes formed endogenously by intermediary metabolism. Drugs that are aldehydes or form reactive aldehyde metabolites that cause side-effect toxicity are also included. The effects of these aldehydes on biological function, their contribution to human diseases, and the role of nucleic acid and protein carbonylation/oxidation in mutagenicity and cytotoxicity mechanisms, respectively, as well as carbonyl signal transduction and gene expression, are reviewed. Aldehyde metabolic activation and detoxication by metabolizing enzymes are also reviewed, as well as the toxicological and anticancer therapeutic effects of metabolizing enzyme inhibitors. The human health risks from clinical and animal research studies are reviewed, including aldehydes as haptens in allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic drug toxicity; the potential carcinogenic risks of the carbonyl body burden; and the toxic effects of aldehydes in liver disease, embryo toxicity/teratogenicity, diabetes/hypertension, sclerosing peritonitis, cerebral ischemia/neurodegenerative diseases, and other aging-associated diseases.
Topics: Aldehydes; Animals; Environmental Pollutants; Enzymes; Humans; Nucleic Acids; Oxidation-Reduction; Proteins; Risk Assessment; Species Specificity; Teratogens
PubMed: 16417045
DOI: 10.1080/10408440591002183 -
Acta Neurologica Taiwanica Dec 2016Aldehydes-induced toxicity has been implicated in many neurodegenerative diseases. Exposure to reactive aldehydes from (1) alcohol and food metabolism; (2) environmental... (Review)
Review
Aldehydes-induced toxicity has been implicated in many neurodegenerative diseases. Exposure to reactive aldehydes from (1) alcohol and food metabolism; (2) environmental pollutants, including car, factory exhausts, smog, pesticides, herbicides; (3) metabolism of neurotransmitters, amino acids and (4) lipid peroxidation of biological membrane from excessive ROS, all contribute to 'aldehydic load' that has been linked to the pathology of neurodegenerative diseases. In particular, the α, β-unsaturated aldehydes derived from lipid peroxidation, 4-hydroxynonenal (4-HNE), DOPAL (MAO product of dopamine), malondialdehyde, acrolein and acetaldehyde, all readily form chemical adductions with proteins, DNA and lipids, thus causing neurotoxicity. Mitochondrial aldehyde dehydrogenase 2 (ALDH 2) is a major aldehyde metabolizing enzyme that protects against deleterious aldehyde buildup in brain, a tissue that has a particularly high mitochondrial content. In this review, we highlight the deleterious effects of increased aldehydic load in the neuropathology of ischemic stroke, Alzheimer's disease and Parkinson's disease. We also discuss evidence for the association between ALDH2 deficiency, a common East Asianspecific mutation, and these neuropathologies. A novel class of small molecule aldehyde dehydrogenase activators (Aldas), represented by Alda-1, reduces neuronal cell death in models of ischemic stroke, Alzheimer's disease and Parkinson's disease. Together, these data suggest that reducing aldeydic load by enhancing the activity of aldehyde dehydrogenases, such as ALDH2, represents as a therapeutic strategy for neurodegenerative diseases.
Topics: Aldehyde Dehydrogenase, Mitochondrial; Aldehydes; Alzheimer Disease; Brain Ischemia; Humans; Parkinson Disease
PubMed: 28382610
DOI: No ID Found -
International Journal of Molecular... Mar 2023Acrolein, a highly reactive α,β-unsaturated aldehyde, is a compound involved in the pathogenesis of many diseases, including neurodegenerative diseases, cardiovascular... (Review)
Review
Acrolein, a highly reactive α,β-unsaturated aldehyde, is a compound involved in the pathogenesis of many diseases, including neurodegenerative diseases, cardiovascular and respiratory diseases, diabetes mellitus, and the development of cancers of various origins. In addition to environmental pollution (e.g., from car exhaust fumes) and tobacco smoke, a serious source of acrolein is our daily diet and improper thermal processing of animal and vegetable fats, carbohydrates, and amino acids. Dietary intake is one of the main routes of human exposure to acrolein, which is a major public health concern. This review focuses on the molecular mechanisms of acrolein activity in the context of its involvement in the pathogenesis of diseases related to the digestive system, including diabetes, alcoholic liver disease, and intestinal cancer.
Topics: Animals; Humans; Aldehydes; Acrolein; Digestive System Diseases; Diet; Diabetes Mellitus
PubMed: 37047550
DOI: 10.3390/ijms24076579 -
Clinical and Laboratory Haematology 1984Formaldehyde, acetaldehyde, malondialdehyde, glutaraldehyde and paraldehyde, when added in vitro to platelet-rich plasma, generate a similar distinct platelet... (Comparative Study)
Comparative Study
Formaldehyde, acetaldehyde, malondialdehyde, glutaraldehyde and paraldehyde, when added in vitro to platelet-rich plasma, generate a similar distinct platelet aggregation response which is dose dependent when measured with a manual visual microscopic technique and by computerized image analysis, 'computerized platelet aggregation analysis'. Light transmission aggregometry did not measure this aggregation in a reliable manner. The aggregating reaction was specific to the aldehyde group and was not seen when the aldehyde was replaced by an alcohol, ketone, or acetate group in the case of acetaldehyde. The maximal aggregating effect of these aldehydes was directly proportional to the number of aldehyde groups per molecule. Aggregation was found to require the presence of plasma, but not von Willebrand's factor.
Topics: Acetaldehyde; Aldehydes; Female; Formaldehyde; Glutaral; Humans; In Vitro Techniques; Male; Malondialdehyde; Middle Aged; Paraldehyde; Platelet Aggregation; Structure-Activity Relationship
PubMed: 6435942
DOI: 10.1111/j.1365-2257.1984.tb00537.x -
Frontiers in Bioscience : a Journal and... Jun 1999A number of systems that generate oxygen free radicals and reactive aldehydic species are activated by excessive ethanol consumption. Recent studies from human... (Review)
Review
A number of systems that generate oxygen free radicals and reactive aldehydic species are activated by excessive ethanol consumption. Recent studies from human alcoholics and from experimental animals have indicated that acetaldehyde and aldehydic products of lipid peroxidation, which are generated in such processes, can bind to proteins forming stable adducts. Adduct formation may lead to several adverse consequences, such as interference with protein function, stimulation of fibrogenesis, and induction of immune responses. The presence of protein adducts in the centrilobular region of the liver in alcohol abusers with an early phase of histological liver damage indicates that adduct formation is one of the key events in the pathogenesis of alcoholic liver disease. Dietary supplementation with fat and/or iron strikingly increases the amount of aldehyde-derived epitopes in the liver together with promotion of fibrogenesis.
Topics: Aldehydes; Animals; Biomarkers; Disease Models, Animal; Ethanol; Extracellular Matrix Proteins; Humans; Liver; Liver Diseases; Oxidative Stress; Protein Binding; Proteins; Rats; Swine
PubMed: 10352137
DOI: 10.2741/niemela -
Food and Chemical Toxicology : An... Jul 2020
Review
Topics: Aldehydes; Humans; Odorants; Perfume; Toxicity Tests
PubMed: 32461162
DOI: 10.1016/j.fct.2020.111430 -
Journal of Environmental Sciences... May 2023Aldehyde and ketone compounds are ubiquitous in the air and prone to adverse effects on human health. Cooking emission is one of the major indoor sources. Aiming to...
Aldehyde and ketone compounds are ubiquitous in the air and prone to adverse effects on human health. Cooking emission is one of the major indoor sources. Aiming to evaluate health risks associated with inhalation exposure to aldehyde and ketone compounds, 13 carbonyl compounds (CCs) released from heating 5 edible oils, 3 seasonings, and 2 dishes were investigated in a kitchen laboratory. For the scenarios of heating five types of oil, aldehydes accounted for 61.1%-78.0% of the total emission, mainly acetaldehyde, acrolein and hexanal. Comparatively, heating oil with added seasonings released greater concentrations of aldehyde and ketone compounds. The concentration enhancement of larger molecular aldehydes was significantly greater. The emission factors of aldehyde and ketone compounds for cooking the dish of chili fried meat were much greater compared to that of tomato fried eggs. Therefore, food materials also had a great impact on the aldehyde and ketone emissions. Acetone and acetaldehyde were the most abundant CCs in the kitchen. Acrolein concentrations ranged from 235.18 to 498.71 µg/m, which was about 100 times greater compared to the guidelines provided by Office of Environmental Health Hazard Assessment (OEHHA). The acetaldehyde inhalation for adults was 856.83-1515.55 µg and 56.23-192.79 µg from exposure to chili fried meat and tomato fried eggs, respectively. This exceeds the reference value of 90 µg/day provided by OEHHA. The findings of this study provided scientific evidences for the roles of cooking emissions on indoor air quality and human health.
Topics: Adult; Humans; Air Pollutants; Ketones; Acrolein; Cooking; Air Pollution, Indoor; Aldehydes; Acetaldehyde; Environmental Monitoring
PubMed: 36522070
DOI: 10.1016/j.jes.2022.05.033 -
Environmental Health Perspectives Dec 1996The hematotoxicity of benzene is mediated by reactive benzene metabolites and possibly by other intermediates including reactive oxygen species. We previously... (Review)
Review
The hematotoxicity of benzene is mediated by reactive benzene metabolites and possibly by other intermediates including reactive oxygen species. We previously hypothesized that ring-opened metabolites may significantly contribute to benzene hematotoxicity. Consistent with this hypothesis, our studies initially demonstrated that benzene is metabolized in vitro to trans-trans-muconaldehyde (MUC), a reactive six-carbon diene dialdehyde, and that MUC is toxic to the bone marrow in a manner similar to benzene. Benzene toxicity most likely involves interactions among several metabolites that operate by different mechanisms to produce more than one biological effect. Our studies indicate that MUC coadministered with hydroquinone is a particularly potent metabolite combination that causes bone marrow damage, suggesting that the involvement of ring-opened metabolites in benzene toxicity may be related to their biological effects in combination with other benzene metabolites. Studies in our laboratory and by others indicate that MUC is metabolized to a variety of compounds by oxidation or reduction of the aldehyde groups. The aldehydic MUC metabolite 6-hydroxy-trans-trans-2,4-hexadienal (CHO-M-OH), similar to MUC but to a lesser extent, is reactive toward glutathione, mutagenic in V79 cells, and hematotoxic in mice. It is formed by monoreduction of MUC, a process that is reversible and could be of biological significance in benzene bone marrow toxicity. The MUC metabolite 6-hydroxy-trans-trans-2,4-hexadienoic (COOH-M-OH) is an end product of MUC metabolism in vitro. Our studies indicate that COOH-M-OH is a urinary metabolite of benzene in mice, a finding that provides further indirect evidence for the in vivo formation of MUC from benzene. Mechanistic studies showed the formation of cis-trans-muconaldehyde in addition to MUC from benzene incubated in a hydroxyl radical-generating Fenton system. These results suggest that the benzene ring is initially opened to cis,cis-muconaldehyde, an unstable isomer that rearranges to cis-trans-muconaldehyde, which further rearranges to trans-trans-muconaldehyde. The latter is not formed from benzene dihydrodiol by reactive oxygen species in a Fenton system that contains reactive oxygen species.
Topics: Aldehydes; Alkadienes; Animals; Benzene; Bone Marrow; In Vitro Techniques; Mice; Molecular Structure; Reactive Oxygen Species
PubMed: 9118893
DOI: 10.1289/ehp.961041195 -
The Analyst Aug 2015We developed a strategy for non-targeted profiling of aldehyde-containing compounds by stable isotope labelling in combination with liquid chromatography-double neutral...
We developed a strategy for non-targeted profiling of aldehyde-containing compounds by stable isotope labelling in combination with liquid chromatography-double neutral loss scan-mass spectrometry (SIL-LC-DNLS-MS) analysis. A pair of stable isotope labelling reagents (4-(2-(trimethylammonio)ethoxy)benzenaminium halide, 4-APC and d4-4-(2-(trimethylammonio)ethoxy)benzenaminium halide, 4-APC-d4) that can selectively label aldehyde-containing compounds were synthesized. The 4-APC and 4-APC-d4 labelled compounds were capable of generating two characteristic neutral fragments of 87 Da and 91 Da, respectively, under collision induced dissociation (CID). Therefore, double neutral loss scans were carried out simultaneously to record the signals of the potential aldehyde-containing compounds. In this respect, the aldehyde-containing compounds from two samples labelled with 4-APC and 4-APC-d4 were ionized at the same time but recorded separately by mass spectrometry. The peak pairs with characteristic mass differences (n × 4 Da) can be readily extracted from the DNLS spectra and assigned as potential aldehyde-containing candidates, which facilitates the identification of the target aldehydes. 4-APC and 4-APC-d4 labelling also dramatically increased detection sensitivities of the derivatives. Using the SIL-LC-DNLS-MS strategy, we successfully profiled the aldehyde-containing compounds in human urine and white wine. Our results showed that 16 and 19 potential aldehyde-containing compounds were discovered in human urine and white wine, respectively. In addition, 5 and 4 aldehyde-containing compounds in human urine and white wine were further identified by comparison with aldehyde standards. Altogether, SIL-LC-DNLS-MS demonstrated to be a promising approach in the identification and relative quantification of aldehyde-containing compounds from complex samples.
Topics: Aldehydes; Chromatography, High Pressure Liquid; Humans; Indicators and Reagents; Isotope Labeling; Lung Neoplasms; Mass Spectrometry; Urinalysis
PubMed: 26086784
DOI: 10.1039/c5an00657k -
Chemical Communications (Cambridge,... Apr 2020We report chemistry suitable for the solid-phase synthesis of DNA-encoded libraries with an unusually high level of structural diversity. The strategy involves...
We report chemistry suitable for the solid-phase synthesis of DNA-encoded libraries with an unusually high level of structural diversity. The strategy involves "exploding" an immobilized aldehyde into a plethora of different functional groups under DNA-compatible conditions.
Topics: Aldehydes; Gene Library; Solid-Phase Synthesis Techniques
PubMed: 32215395
DOI: 10.1039/d0cc01474e