Articles de revues : « Alcohol metabolite »

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Xu, Jiayang, Xiaoyue Zhang, Lili Yan, Zhichao Zhang, Jing Wei, Luqi Li et Qiang Zhang. « Insight into Lotusine and Puerarin in Repairing Alcohol-Induced Metabolic Disorder Based on UPLC-MS/MS ». International Journal of Molecular Sciences 23, n^o 18 (8 septembre 2022) : 10385. http://dx.doi.org/10.3390/ijms231810385.

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Alcohol is an essential element in human culture. However, alcoholism has contributed to numerous health issues, including alcoholic fatty liver and sudden death. We found that the alkaloid lotusine possessed hepato- and neuroprotection against alcohol injuries. Lotusine showed comparable protective effects to puerarin, a widely recognized antagonist against alcohol damage. To better understand the metabolic response to alcohol injury and antagonist molecules, we applied sensitive zebrafish and LC-ESI-MS to collect metabolites related to alcohol, puerarin and lotusine exposure. LC-MS identified 119 metabolites with important physiological roles. Differential metabolomic analysis showed that alcohol caused abnormal expression of 82 metabolites (60 up-regulated and 22 down-regulated). These differential metabolites involved 18 metabolic pathways and modules, including apoptosis, necroptosis, nucleotide and fatty acid metabolism. Puerarin reversed seven metabolite variations induced by alcohol, which were related to necroptosis and sphingolipid metabolism. Lotusine was found to repair five metabolites disorders invoked by alcohol, mainly through nucleotide metabolism and glutathione metabolism. In phenotypic bioassay, lotusine showed similar activities to puerarin in alleviating behavioral abnormalities, neuroapoptosis and hepatic lipid accumulation induced by alcohol exposure. Our findings provided a new antagonist, lotusine, for alcohol-induced damage and explored the roles in repairing abnormal metabolism.

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Lapadatescu, Carmen, Christian Giniès, Jean-Luc Le Quéré et Pascal Bonnarme. « Novel Scheme for Biosynthesis of Aryl Metabolites from l-Phenylalanine in the FungusBjerkandera adusta ». Applied and Environmental Microbiology 66, n^o 4 (1 avril 2000) : 1517–22. http://dx.doi.org/10.1128/aem.66.4.1517-1522.2000.

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ABSTRACT Aryl metabolite biosynthesis was studied in the white rot fungusBjerkandera adusta cultivated in a liquid medium supplemented with l-phenylalanine. Aromatic compounds were analyzed by gas chromatography-mass spectrometry following addition of labelled precursors (14C- and 13C-labelledl-phenylalanine), which did not interfere with fungal metabolism. The major aromatic compounds identified were benzyl alcohol, benzaldehyde (bitter almond aroma), and benzoic acid. Hydroxy- and methoxybenzylic compounds (alcohols, aldehydes, and acids) were also found in fungal cultures. Intracellular enzymatic activities (phenylalanine ammonia lyase, aryl-alcohol oxidase, aryl-alcohol dehydrogenase, aryl-aldehyde dehydrogenase, lignin peroxidase) and extracellular enzymatic activities (aryl-alcohol oxidase, lignin peroxidase), as well as aromatic compounds, were detected in B. adusta cultures. Metabolite formation required de novo protein biosynthesis. Our results show that l-phenylalanine was deaminated to trans-cinnamic acid by a phenylalanine ammonia lyase and trans-cinnamic acid was in turn converted to aromatic acids (phenylpyruvic, phenylacetic, mandelic, and benzoylformic acids); benzaldehyde was a metabolic intermediate. These acids were transformed into benzaldehyde, benzyl alcohol, and benzoic acid. Our findings support the hypothesis that all of these compounds are intermediates in the biosynthetic pathway froml-phenylalanine to aryl metabolites. Additionally,trans-cinnamic acid can also be transformed via β-oxidation to benzoic acid. This was confirmed by the presence of acetophenone as a β-oxidation degradation intermediate. To our knowledge, this is the first time that a β-oxidation sequence leading to benzoic acid synthesis has been found in a white rot fungus. A novel metabolic scheme for biosynthesis of aryl metabolites froml-phenylalanine is proposed.

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George, Donald A. « Permethrin and Its Two Metabolite Residues in Seven Agricultural Crops ». Journal of AOAC INTERNATIONAL 68, n^o 6 (1 novembre 1985) : 1160–63. http://dx.doi.org/10.1093/jaoac/68.6.1160.

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Abstract Metabolite residues of permethrin are not reported in the literature for most agricultural crops. This paper reports residues of permethrin and its 2 metabolites (dichlorovinyl acid and metaphenoxybenzyl alcohol) in 7 different agricultural crops (Chinese cabbage, spinach, asparagus, raspberries, green peas, turnip roots, and turnip greens). Permethrin residues declined approximately 85% within 7 days after treatment in all crops. In most cases, the acid metabolite residues peaked at 3 days, and declined after that. Translocation of residues into turnip roots was very slight; the average was less than 0.05 ppm for permethrin and alcohol metabolite residues and none was detected for the acid metabolite residue. Permethrin residues in the turnip greens averaged approximately 2 ppm for the 0.112 kg ai/ha treatment, and 6 ppm for the 0.224 kg ai/ha treatment.

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Hardikar, Sheetal, Richard D. Albrechtsen, David Achaintre, Tengda Lin, Svenja Pauleck, Mary Playdon, Andreana N. Holowatyj et al. « Impact of Pre-Blood Collection Factors on Plasma Metabolomic Profiles ». Metabolites 10, n^o 5 (21 mai 2020) : 213. http://dx.doi.org/10.3390/metabo10050213.

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Demographic, lifestyle and biospecimen-related factors at the time of blood collection can influence metabolite levels in epidemiological studies. Identifying the major influences on metabolite concentrations is critical to designing appropriate sample collection protocols and considering covariate adjustment in metabolomics analyses. We examined the association of age, sex, and other short-term pre-blood collection factors (time of day, season, fasting duration, physical activity, NSAID use, smoking and alcohol consumption in the days prior to collection) with 133 targeted plasma metabolites (acylcarnitines, amino acids, biogenic amines, sphingolipids, glycerophospholipids, and hexoses) among 108 individuals that reported exposures within 48 h before collection. The differences in mean metabolite concentrations were assessed between groups based on pre-collection factors using two-sided t-tests and ANOVA with FDR correction. Percent differences in metabolite concentrations were negligible across season, time of day of collection, fasting status or lifestyle behaviors at the time of collection, including physical activity or the use of tobacco, alcohol or NSAIDs. The metabolites differed in concentration between the age and sex categories for 21.8% and 14.3% metabolites, respectively. In conclusion, extrinsic factors in the short period prior to collection were not meaningfully associated with concentrations of selected endogenous metabolites in a cross-sectional sample, though metabolite concentrations differed by age and sex. Larger studies with more coverage of the human metabolome are warranted.

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Langenau, Julia, Kolade Oluwagbemigun, Christian Brachem, Wolfgang Lieb, Romina di Giuseppe, Anna Artati, Gabi Kastenmüller, Leonie Weinhold, Matthias Schmid et Ute Nöthlings. « Blood Metabolomic Profiling Confirms and Identifies Biomarkers of Food Intake ». Metabolites 10, n^o 11 (17 novembre 2020) : 468. http://dx.doi.org/10.3390/metabo10110468.

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Metabolomics can be a tool to identify dietary biomarkers. However, reported food-metabolite associations have been inconsistent, and there is a need to explore further associations. Our aims were to confirm previously reported food-metabolite associations and to identify novel food-metabolite associations. We conducted a cross-sectional analysis of data from 849 participants (57% men) of the PopGen cohort. Dietary intake was obtained using FFQ and serum metabolites were profiled by an untargeted metabolomics approach. We conducted a systematic literature search to identify previously reported food-metabolite associations and analyzed these associations using linear regression. To identify potential novel food-metabolite associations, datasets were split into training and test datasets and linear regression models were fitted to the training datasets. Significant food-metabolite associations were evaluated in the test datasets. Models were adjusted for covariates. In the literature, we identified 82 food-metabolite associations. Of these, 44 associations were testable in our data and confirmed associations of coffee with 12 metabolites, of fish with five, of chocolate with two, of alcohol with four, and of butter, poultry and wine with one metabolite each. We did not identify novel food-metabolite associations; however, some associations were sex-specific. Potential use of some metabolites as biomarkers should consider sex differences in metabolism.

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Homann. « Alcohol and cancer ». Therapeutische Umschau 57, n^o 4 (1 avril 2000) : 236–40. http://dx.doi.org/10.1024/0040-5930.57.4.236.

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Alkohol stellt neben Rauchen den Hauptrisikofaktor in der Entstehung bösartiger Tumoren im oberen Verdauungstrakt (Mund-Rachen-Bereich, Kehlkopf und Speiseröhre) dar. Neben dem hepatozellulären Karzinom konnte durch neuere Studien gezeigt werden, daß Alkohol auch ein Risikofaktor für die Entwicklung eines Malignoms in Brust und Kolon ist. Tierexperimentelle Daten legen nahe, daß Alkohol kein Karzinogen ist, wohl aber unter bestimmten Bedingungen als ein Tumorpromoter und Kokarzinogen wirkt. Neuere Studien lassen den Schluß zu, daß ein Großteil der karzinogenen Wirkung von Alkohol nicht durch Alkohol selbst, sondern durch seinen ersten Metaboliten Azetaldehyd vermittelt wird. Weitere, für alle Tumorarten zutreffende systemische, tumorfördernde Wirkungen von Alkohol umfassen eine erhöhte Löslichkeit anderer Karzinogene, Induktion des Cytochrom P450IIE1 mit Bildung toxischer Metabolite und Aktivierung von Prokarzinogenen, verminderte Bioverfügbarkeit krebsprotektiver Substanzen beim Alkoholiker, gestörte Detoxifikation durch Alkohol und eine herabgesetzte Immunfunktion.

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Hasken, Julie M., Marlene M. de Vries, Anna-Susan Marais, Philip A. May, Charles D. H. Parry, Soraya Seedat, Sandra M. Mooney et Susan M. Smith. « Untargeted Metabolome Analysis of Alcohol-Exposed Pregnancies Reveals Metabolite Differences That Are Associated with Infant Birth Outcomes ». Nutrients 14, n^o 24 (17 décembre 2022) : 5367. http://dx.doi.org/10.3390/nu14245367.

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Prenatal alcohol exposure can produce offspring growth deficits and is a leading cause of neurodevelopmental disability. We used untargeted metabolomics to generate mechanistic insight into how alcohol impairs fetal development. In the Western Cape Province of South Africa, 52 women between gestational weeks 5–36 (mean 18.5 ± 6.5) were recruited, and they provided a finger-prick fasting bloodspot that underwent mass spectrometry. Metabolomic data were analyzed using partial least squares-discriminant analyses (PLS-DA) to identify metabolites that correlated with alcohol exposure and infant birth outcomes. Women who consumed alcohol in the past seven days were distinguished by a metabolite profile that included reduced sphingomyelins, cholesterol, and pregnenolones, and elevated fatty acids, acyl and amino acyl carnitines, and androsterones. Using PLS-DA, 25 of the top 30 metabolites differentiating maternal groups were reduced by alcohol with medium-chain free fatty acids and oxidized sugar derivatives having the greatest influence. A separate ortho-PLS-DA analysis identified a common set of 13 metabolites that were associated with infant length, weight, and head circumference. These included monoacylglycerols, glycerol-3-phosphate, and unidentified metabolites, and most of their associations were negative, implying they represent processes having adverse consequences for fetal development.

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Jala, Venkatakrishna R., Rajbir Singh, Sandeep Chandrashekharappa, Swathi Joshi-Barve, Craig McClain, Bodduluri Bodduluri et Praveen Kumar Vemula. « Gut microbial metabolites as therapeutics to treat of alcoholic liver disease ». Journal of Immunology 204, n^o 1_Supplement (1 mai 2020) : 83.17. http://dx.doi.org/10.4049/jimmunol.204.supp.83.17.

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Abstract Alcoholic liver disease (ALD) is resultant of excessive consumption of alcohol. ALD is the world’s third largest risk factor for diseases and disabilities and accounting for 5.9% of all deaths worldwide. ALD patients exhibit increased gut permeability, gut microbial dysbiosis, endotoxemia and hepatic steatosis. Recent studies, unequivocally demonstrated the importance of gut microbiota and their metabolites in regulating host pathophysiology. Urolithin A (UroA) is a gut microbial metabolite derived from dietary ellagic acid and ellagitannins containing foods. Previously, we showed that UroA act as an AhR agonist and activate AhR-Nrf2 pathways to induce tight junction proteins and enhance gut barrier function. In the current study, we tested the hypothesis that correcting gut barrier dysfunction, blocking inflammation and reducing hepatic steatosis simultaneously by UroA would provide better therapeutic options to treat ALD. Our studies suggested that UroA significantly induced expression of tight junction (TJ) proteins (Occludin, Cldn4 and ZO1) in AhR-Nrf2 dependent manner and protected from alcohol-induced downregulation of TJ proteins and reduced gut barrier leakage. Further, UroA attenuated ALD pathogenesis in both acute and chronic experimental mouse models by reducing alcohol induced barrier permeability, systemic endotoxin levels and inflammatory mediators. In these models, UroA treatment also significantly reduced alcohol induced liver ALT/AST levels, inflammatory mediators (TNF-α, IL-6, IL-1β) and triglyceride levels as well as prevented liver damage. In summary, these studies highlight that the mechanisms of microbial metabolite, UroA and its multi-pronged beneficial effects in attenuating ALD.

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Wang, Ning, Bogdan Szostek, Robert C. Buck, Patrick W. Folsom, Lisa M. Sulecki et John T. Gannon. « 8-2 Fluorotelomer alcohol aerobic soil biodegradation : Pathways, metabolites, and metabolite yields ». Chemosphere 75, n^o 8 (mai 2009) : 1089–96. http://dx.doi.org/10.1016/j.chemosphere.2009.01.033.

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Azizov, Vugar, et Mario M. Zaiss. « Alcohol Consumption in Rheumatoid Arthritis : A Path through the Immune System ». Nutrients 13, n^o 4 (16 avril 2021) : 1324. http://dx.doi.org/10.3390/nu13041324.

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Benefits and harms of different components of human diet have been known for hundreds of years. Alcohol is one the highest consumed, abused, and addictive substances worldwide. Consequences of alcohol abuse are increased risks for diseases of the cardiovascular system, liver, and nervous system, as well as reduced immune system function. Paradoxically, alcohol has also been a consistent protective factor against the development of autoimmune diseases such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (RA). Here, we focused on summarizing current findings on the effects of alcohol, as well as of its metabolites, acetaldehyde and acetate, on the immune system and RA. Heavy or moderate alcohol consumption can affect intestinal barrier integrity, as well as the microbiome, possibly contributing to RA. Additionally, systemic increase in acetate negatively affects humoral immune response, diminishing TFH cell as well as professional antigen-presenting cell (APC) function. Hence, alcohol consumption has profound effects on the efficacy of vaccinations, but also elicits protection against autoimmune diseases. The mechanism of alcohol’s negative effects on the immune system is multivariate. Future studies addressing alcohol and its metabolite acetate’s effect on individual components of the immune system remains crucial for our understanding and development of novel therapeutic pathways.

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Vatsalya, Vatsalya, Maiying Kong, Leila Gobejishvili, Wei-Yang Chen, Sanjay Srivastava, Shirish Barve, Craig McClain et Swati Joshi-Barve. « Urinary acrolein metabolite levels in severe acute alcoholic hepatitis patients ». American Journal of Physiology-Gastrointestinal and Liver Physiology 316, n^o 1 (1 janvier 2019) : G115—G122. http://dx.doi.org/10.1152/ajpgi.00209.2018.

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Alcohol-associated liver disease (ALD) remains a major health concern worldwide. Alcohol consumption gives rise to reactive/toxic acrolein, a pathogenic mediator of liver injury in experimental ALD. Elevated acrolein adducts and metabolites are detectable in blood and urine. This study evaluates the major urinary acrolein metabolite, 3-hydroxypropylmercapturic acid (HPMA), in patients with acute alcoholic hepatitis (AAH) and examines its association with disease severity and markers of hepatic inflammation and injury. Urine HPMA was significantly higher in patients with severe [model for end-stage liver disease (MELD) ≥ 20] AAH compared with nonsevere AAH (MELD ≤ 19) or non-alcohol-consuming controls, suggesting that urine HPMA is a novel noninvasive biomarker in severe AAH. The association between HPMA and MELD in patients with AAH was nonlinear. In patients with nonsevere AAH, there was a positive trend, although not significant, whereas in severe AAH the association was negative, indicative of extensive injury and glutathione depletion. Consistent with the multifactorial etiology of ALD, our data identified strong combined effects of HPMA and proinflammatory cytokines on hepatocyte cell death, thereby supporting the pathogenic role of acrolein in liver injury. HPMA, together with IL-1β, showed robust associations with cytokeratin 18 caspase-cleaved fragment (CK18-M30; adjusted R2 = 0.812, P = 0.016) and cytokeratin 18 full-length protein (CK18-M65; adjusted R2 = 0.670, P = 0.048); similarly, HPMA, with IL-8, correlated with CK18-M30 (adjusted R2 = 0.875, P = 0.007) and CK18-M65 (adjusted R2 = 0.831, P = 0.013). The apoptosis index (CK18-M30:CK18-M65 ratio) strongly correlated with HPMA, together with IL-1β (adjusted R2 = 0.777, P = 0.022) or tumor necrosis factor-α (TNFα; adjusted R2 = 0.677, P = 0.046). In patients with severe AAH, IL-1β, IL-8, and TNFα are the predominant proinflammatory cytokines that interact with HPMA and play important mediating roles in influencing the extent/pattern of liver cell death. NEW & NOTEWORTHY This is the first study to examine the urinary acrolein metabolite 3-hydroxypropylmercapturic acid (HPMA) in alcoholic liver disease. HPMA was higher in patients with severe acute alcoholic hepatitis (AAH) compared with controls or nonsevere AAH and may be a novel selective, noninvasive biomarker for severe AAH. Consistent with the multifactorial etiology of alcohol-associated liver disease, we identified strong combined effects of HPMA and proinflammatory cytokines (IL-1β, IL-8, and TNFα) on the extent/pattern of liver cell death, thereby supporting the pathogenic role of acrolein.

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Goecke, Tamme W., Pascal Burger, Peter A. Fasching, Abdulsallam Bakdash, Anne Engel, Lothar Häberle, Franziska Voigt et al. « Meconium Indicators of Maternal Alcohol Abuse during Pregnancy and Association with Patient Characteristics ». BioMed Research International 2014 (2014) : 1–11. http://dx.doi.org/10.1155/2014/702848.

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Aim. Identification of women with moderate alcohol abuse during pregnancy is difficult. We correlated self-reported alcohol consumption during pregnancy and patient characteristics with objective alcohol indicators measured in fetal meconium.Methods. A total of 557 women singleton births and available psychological tests, obstetric data and meconium samples were included in statistical analysis. Alcohol metabolites (fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG)), were determined from meconium and correlated with patient characteristics.Results. We found that 21.2% of the 557 participants admitted low-to-moderate alcohol consumption during pregnancy. Of the parameters analyzed from meconium, only EtG showed an association with alcohol history (P<0.01). This association was inverse in cases with EtG value above 120 ng/g. These values indicate women with most severe alcohol consumption, who obviously denied having consumed alcohol during pregnancy. No other associations between socioeconomic or psychological characteristics and the drinking status (via meconium alcohol metabolites) could be found.Conclusion. Women who drink higher doses of ethanol during pregnancy, according to metabolite measures in meconium, might be less likely to admit alcohol consumption. No profile of socioeconomic or psychological characteristics of those women positively tested via meconium could be established.

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Rosales, Corina, Baiba K. Gillard, Antonio M. Gotto et Henry J. Pownall. « The Alcohol–High-Density Lipoprotein Athero-Protective Axis ». Biomolecules 10, n^o 7 (1 juillet 2020) : 987. http://dx.doi.org/10.3390/biom10070987.

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Ingestion of alcohol is associated with numerous changes in human energy metabolism, especially that of plasma lipids and lipoproteins. Regular moderate alcohol consumption is associated with reduced atherosclerotic cardiovascular disease (ASCVD), an effect that has been attributed to the concurrent elevations of plasma high-density lipoprotein-cholesterol (HDL-C) concentrations. More recent evidence has accrued against the hypothesis that raising plasma HDL concentrations prevents ASCVD so that other metabolic processes associated with alcohol consumption have been considered. This review explored the roles of other metabolites induced by alcohol consumption—triglyceride-rich lipoproteins, non-esterified free fatty acids, and acetate, the terminal alcohol metabolite in athero-protection: Current evidence suggests that acetate has a key role in athero-protection but additional studies are needed.

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Goto, Tatsuhiko, Hiroki Mori, Shunsuke Shiota et Shozo Tomonaga. « Metabolomics Approach Reveals the Effects of Breed and Feed on the Composition of Chicken Eggs ». Metabolites 9, n^o 10 (13 octobre 2019) : 224. http://dx.doi.org/10.3390/metabo9100224.

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Chicken eggs provide essential nutrients to consumers around the world. Although both genetic and environmental factors influence the quality of eggs, it is unclear how these factors affect the egg traits including egg metabolites. In this study, we investigated breed and feed effects on 10 egg traits, using two breeds (Rhode Island Red and Australorp) and two feed conditions (mixed feed and fermented feed). We also used gas chromatography–mass spectrometry (GC–MS/MS) to analyze 138 yolk and 132 albumen metabolites. Significant breed effects were found on yolk weight, eggshell weight, eggshell colors, and one albumen metabolite (ribitol). Three yolk metabolites (erythritol, threitol, and urea) and 12 albumen metabolites (erythritol, threitol, ribitol, linoleic acid, isoleucine, dihydrouracil, 4-hydroxyphenyllactic acid, alanine, glycine, N-butyrylglycine, pyruvic acid, and valine) were significantly altered by feed, and a significant interaction between breed and feed was discovered in one albumen metabolite (N-butyrylglycine). Yolk and albumin had higher levels of sugar alcohols when hens were fed a fermented diet, which indicates that sugar alcohol content can be transferred from diet into eggs. Linoleic acid was also enriched in albumen under fermented feed conditions. This study shows that yolk and albumen metabolites will be affected by breed and feed, which is the first step towards manipulating genetic and environmental factors to create “designer eggs.”

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Setiawati, Tia, Alma Ayalla, Mohamad Nurzaman, Valentina A. Kusumaningtyas et Ichsan Bari. « Analysis of Secondary Metabolites of Shoot, Callus Culture and Field Plant of Chrysanthemum morifolium Ramat ». Jurnal ILMU DASAR 21, n^o 1 (21 janvier 2020) : 1. http://dx.doi.org/10.19184/jid.v21i1.8665.

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The chrysanthemum plant (Chrysanthemum morifolium Ramat.) contains many secondary metabolites such as flavonoids and various volatile compounds that can be utilized as drugs. Tissue culture can be an alternative to enhance the production of certain secondary metabolite. The study aimed to determine the types of secondary metabolites that contained in shoot culture, callus and field plants of C. morifolium. The research method was exploration in the laboratory to analyze and compare the content of secondary metabolite from shoot culture, callus and field plants of C. morifolium. Callus was induced by explants of C. morifolium plantlet stems and leaves respectively on MS medium with an addition of 3 ppm 2,4-D + 2 ppm kinetin and 4 ppm 2,4-D. For shoot culture, single nodule explants with one leaf were planted on MS media with the addition of 1 ppm BAP. The secondary metabolite compouds were analized and identified by GC-MS (Gas Chromatography-Mass Spectrometry). The results showed that various types of secondary metabolites contained in shoot culture, callus and field plants of C. morifolium. In callus culture from leaf explants, four compounds from groups of alcohol, acetic acid and organosilicon were identified, whereas in callus culture from stem explants were identified eight compounds from aldehydes, esters, alkanes, and carboxylic acids group. In the shoot culture, nine compounds of alcohol, ketone, aldehyde, cycloalkane and organosilicon group were identified, while in the field plants five compounds were identified from the cycloalkanes, ketones, organoborones and organosilicon group. Some detected compounds have a potential as precursors of alkaloid, phenolic, and flavonoid.Keywords: chrysanthemum, culture, shoots, callus, secondary metabolites.

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Shrestha, Riya, Pil Cho, Sanjita Paudel, Aarajana Shrestha, Mi Kang, Tae Jeong, Eung-Seok Lee et Sangkyu Lee. « Exploring the Metabolism of Loxoprofen in Liver Microsomes : The Role of Cytochrome P450 and UDP-Glucuronosyltransferase in Its Biotransformation ». Pharmaceutics 10, n^o 3 (2 août 2018) : 112. http://dx.doi.org/10.3390/pharmaceutics10030112.

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Loxoprofen, a propionic acid derivative, non-steroidal anti-inflammatory drug (NSAID) is a prodrug that is reduced to its active metabolite, trans-alcohol form (Trans-OH) by carbonyl reductase enzyme in the liver. Previous studies demonstrated the hydroxylation and glucuronidation of loxoprofen. However, the specific enzymes catalyzing its metabolism have yet to be identified. In the present study, we investigated metabolic enzymes, such as cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT), which are involved in the metabolism of loxoprofen. Eight microsomal metabolites of loxoprofen were identified, including two alcohol metabolites (M1 and M2), two mono-hydroxylated metabolites (M3 and M4), and four glucuronide conjugates (M5, M6, M7, and M8). Based on the results for the formation of metabolites when incubated in dexamethasone-induced microsomes, incubation with ketoconazole, and human recombinant cDNA-expressed cytochrome P450s, we identified CYP3A4 and CYP3A5 as the major CYP isoforms involved in the hydroxylation of loxoprofen (M3 and M4). Moreover, we identified that UGT2B7 is the major UGT isoform catalyzing the glucuronidation of loxoprofen and its alcoholic metabolites. Further experimental studies should be carried out to determine the potency and toxicity of these identified metabolites of loxoprofen, in order to fully understand of mechanism of loxoprofen toxicity.

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Sarmanaev, S. Kh, I. V. Zaborskikh, V. B. Simonenko et P. A. Dulin. « Diagnostics of methyl alcohol intoxication : possibilities and prospects ». Clinical Medicine (Russian Journal) 95, n^o 5 (8 juin 2017) : 432–37. http://dx.doi.org/10.18821/0023-2149-2017-95-5-432-437.

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Intake of toxic alcohols especially methyl alcohol posses a serious threat to health. Despite relatively low toxicity of methanol (hazard class III), its metabolite formic acid resulting from biotransformation of methyl alcohol by alcohol dehydrogenase is ranked among substances creating a high risk of toxic action. The long period of methanol toxification (~48 hr) makes difficult diagnostics of intoxication and therefore delays provision of emergency medical aid. It imposes high requirements on express diagnostics of methyl alcohol intoxication (Т51.1 ICD-10). The main diagnostic modality - routine evaluation of osmolar and anion gaps, has advantages and disadvantages. Drawbacks of emergency medical aid to the victims of methyl alcohol intoxication necessitates the search for new diagnostic options some of which sre discussed in the present article.

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Langenau, Boeing, Bergmann, Nöthlings et Oluwagbemigun. « The Association between Alcohol Consumption and Serum Metabolites and the Modifying Effect of Smoking ». Nutrients 11, n^o 10 (1 octobre 2019) : 2331. http://dx.doi.org/10.3390/nu11102331.

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Alcohol consumption is an important lifestyle factor that is associated with several health conditions and a behavioral link with smoking is well established. Metabolic alterations after alcohol consumption have yet to be comprehensively investigated. We studied the association of alcohol consumption with metabolite patterns (MPs) among 2433 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study, and a potential modification by smoking. Alcohol consumption was self-reported through dietary questionnaires and serum metabolites were measured by a targeted approach. The metabolites were summarized as MPs using the treelet transform analysis (TT). We fitted linear models with alcohol consumption continuously and in five categories. We stratified the continuously modelled alcohol consumption by smoking status. All models were adjusted for potential confounders. Among men, alcohol consumption was positively associated with six MPs and negatively associated with one MP. In women, alcohol consumption was inversely associated with one MP. Heavy consumers differed from other consumers with respect to the “Long and short chain acylcarnitines” MP. Our findings suggest that long and short chain acylcarnitines might play an important role in the adverse effects of heavy alcohol consumption on chronic diseases. The relations seem to depend on gender and smoking status.

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Rumgay, Harriet, Neil Murphy, Pietro Ferrari et Isabelle Soerjomataram. « Alcohol and Cancer : Epidemiology and Biological Mechanisms ». Nutrients 13, n^o 9 (11 septembre 2021) : 3173. http://dx.doi.org/10.3390/nu13093173.

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Approximately 4% of cancers worldwide are caused by alcohol consumption. Drinking alcohol increases the risk of several cancer types, including cancers of the upper aerodigestive tract, liver, colorectum, and breast. In this review, we summarise the epidemiological evidence on alcohol and cancer risk and the mechanistic evidence of alcohol-mediated carcinogenesis. There are several mechanistic pathways by which the consumption of alcohol, as ethanol, is known to cause cancer, though some are still not fully understood. Ethanol’s metabolite acetaldehyde can cause DNA damage and block DNA synthesis and repair, whilst both ethanol and acetaldehyde can disrupt DNA methylation. Ethanol can also induce inflammation and oxidative stress leading to lipid peroxidation and further DNA damage. One-carbon metabolism and folate levels are also impaired by ethanol. Other known mechanisms are discussed. Further understanding of the carcinogenic properties of alcohol and its metabolites will inform future research, but there is already a need for comprehensive alcohol control and cancer prevention strategies to reduce the burden of cancer attributable to alcohol.

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Prativi, Mahensa Billqys Nurhayati, Dea Indriani Astuti, Sastia Prama Putri, Walter A. Laviña, Eiichiro Fukusaki et Pingkan Aditiawati. « Metabolite Changes in Indonesian Tempe Production from Raw Soybeans to Over-Fermented Tempe ». Metabolites 13, n^o 2 (17 février 2023) : 300. http://dx.doi.org/10.3390/metabo13020300.

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Tempe is fermented soybean from Java, Indonesia, that can serve as a functional food due to its high nutritional content and positive impact on health. Although the tempe fermentation process is known to affect its nutrient content, changes in the metabolite profile during tempe production have not been comprehensively examined. Thus, this research applied a metabolomics approach to investigate the metabolite profile in each step of tempe production, from soybean soaking to over-fermentation. Fourteen samples of raw soybeans, i.e., soaked soybeans (24 h), steamed soybeans, fungal fermented soybeans, and over-fermented soybeans (up to 72 h), were collected. Untargeted metabolomics by gas chromatography/mass spectrometry (GC–MS) was used to determine soybean transformations from various fermentation times and identify disparity-related metabolites. The results showed that soybeans samples clustered together on the basis of the different fermentation steps. The results also showed that sugar, sugar alcohol, organic acids, and amino acids, as well as fermentation time, contributed to the soybean metabolite profile transformations. During the fermentation of tempe, sugars and sugar alcohols accumulated at the beginning of the process before gradually decreasing as fermentation progressed. Specifically, at the beginning of the fermentation, gentiobiose, galactinol, and glucarate were accumulated, and several metabolites such as glutamine, 4-hydroxyphenylacetic acid, and homocysteine increased along with the progression of fermentation. In addition, notable isoflavones daidzein and genistein increased from 24 h of fermentation until 72 h. This is the first report that provides a complete description of the metabolic profile of the tempe production from soybean soaking to over-fermentation. Through this study, the dynamic changes at each step of tempe production were revealed. This information can be beneficial to the tempe industry for the improvement of product quality based on metabolite profiling.

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Simon, Liz, Flavia M. Souza-Smith et Patricia E. Molina. « Alcohol-Associated Tissue Injury : Current Views on Pathophysiological Mechanisms ». Annual Review of Physiology 84, n^o 1 (10 février 2022) : 87–112. http://dx.doi.org/10.1146/annurev-physiol-060821-014008.

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At-risk alcohol use is a major contributor to the global health care burden and leads to preventable deaths and diseases including alcohol addiction, alcoholic liver disease, cardiovascular disease, diabetes, traumatic injuries, gastrointestinal diseases, cancers, and fetal alcohol syndrome. Excessive and frequent alcohol consumption has increasingly been linked to alcohol-associated tissue injury and pathophysiology, which have significant adverse effects on multiple organ systems. Extensive research in animal and in vitro models has elucidated the salient mechanisms involved in alcohol-induced tissue and organ injury. In some cases, these pathophysiological mechanisms are shared across organ systems. The major alcohol- and alcohol metabolite–mediated mechanisms include oxidative stress, inflammation and immunometabolic dysregulation, gut leak and dysbiosis, cell death, extracellular matrix remodeling, endoplasmic reticulum stress, mitochondrial dysfunction, and epigenomic modifications. These mechanisms are complex and interrelated, and determining the interplay among them will make it possible to identify how they synergistically or additively interact to cause alcohol-mediated multiorgan injury. In this article, we review the current understanding of pathophysiological mechanisms involved in alcohol-induced tissue injury.

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Drogan, Dagmar, Warwick B. Dunn, Wanchang Lin, Brian Buijsse, Matthias B. Schulze, Claudia Langenberg, Marie Brown et al. « Untargeted Metabolic Profiling Identifies Altered Serum Metabolites of Type 2 Diabetes Mellitus in a Prospective, Nested Case Control Study ». Clinical Chemistry 61, n^o 3 (1 mars 2015) : 487–97. http://dx.doi.org/10.1373/clinchem.2014.228965.

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Abstract BACKGROUND Application of metabolite profiling could expand the etiological knowledge of type 2 diabetes mellitus (T2D). However, few prospective studies apply broad untargeted metabolite profiling to reveal the comprehensive metabolic alterations preceding the onset of T2D. METHODS We applied untargeted metabolite profiling in serum samples obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort comprising 300 individuals who developed T2D after a median follow-up time of 6 years and 300 matched controls. For that purpose, we used ultraperformance LC-MS with a protocol specifically designed for large-scale metabolomics studies with regard to robustness and repeatability. After multivariate classification to select metabolites with the strongest contribution to disease classification, we applied multivariable-adjusted conditional logistic regression to assess the association of these metabolites with T2D. RESULTS Among several alterations in lipid metabolism, there was an inverse association with T2D for metabolites chemically annotated as lysophosphatidylcholine(dm16:0) and phosphatidylcholine(O-20:0/O-20:0). Hexose sugars were positively associated with T2D, whereas higher concentrations of a sugar alcohol and a deoxyhexose sugar reduced the odds of diabetes by approximately 60% and 70%, respectively. Furthermore, there was suggestive evidence for a positive association of the circulating purine nucleotide isopentenyladenosine-5′-monophosphate with incident T2D. CONCLUSIONS This study constitutes one of the largest metabolite profiling approaches of T2D biomarkers in a prospective study population. The findings might help generate new hypotheses about diabetes etiology and develop further targeted studies of a smaller number of potentially important metabolites.

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Grenville, Zoe S., Urwah Noor, Mathilde His, Vivian Viallon, Sabina Rinaldi, Elom K. Aglago, Pilar Amiano et al. « Diet and BMI Correlate with Metabolite Patterns Associated with Aggressive Prostate Cancer ». Nutrients 14, n^o 16 (12 août 2022) : 3306. http://dx.doi.org/10.3390/nu14163306.

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Three metabolite patterns have previously shown prospective inverse associations with the risk of aggressive prostate cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC). Here, we investigated dietary and lifestyle correlates of these three prostate cancer-related metabolite patterns, which included: 64 phosphatidylcholines and three hydroxysphingomyelins (Pattern 1), acylcarnitines C18:1 and C18:2, glutamate, ornithine, and taurine (Pattern 2), and 8 lysophosphatidylcholines (Pattern 3). In a two-stage cross-sectional discovery (n = 2524) and validation (n = 518) design containing 3042 men free of cancer in EPIC, we estimated the associations of 24 dietary and lifestyle variables with each pattern and the contributing individual metabolites. Associations statistically significant after both correction for multiple testing (False Discovery Rate = 0.05) in the discovery set and at p < 0.05 in the validation set were considered robust. Intakes of alcohol, total fish products, and its subsets total fish and lean fish were positively associated with Pattern 1. Body mass index (BMI) was positively associated with Pattern 2, which appeared to be driven by a strong positive BMI-glutamate association. Finally, both BMI and fatty fish were inversely associated with Pattern 3. In conclusion, these results indicate associations of fish and its subtypes, alcohol, and BMI with metabolite patterns that are inversely associated with risk of aggressive prostate cancer.

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Petelkov, Ivan, Vesela Shopska, Rositsa Denkova-Kostova, Kristina Ivanova, Georgi Kostov et Velislava Lyubenova. « Investigation of Fermentation Regimes for the Production of Low-alcohol and Non-alcohol Beers ». Periodica Polytechnica Chemical Engineering 65, n^o 2 (11 janvier 2021) : 229–37. http://dx.doi.org/10.3311/ppch.15975.

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The combination of modified mashing method and arrested fermentation for the production of low-alcohol and non-alcohol beers was studied. Therefore, five regimes for fermentation of wort with reduced fermentable sugar content with top-fermenting yeast strain at low temperatures and pitching rates were investigated. According to the fermentation dynamic results the decrease in the fermentation temperature from 10 °C to 5 °C at pitching rate of 109 Colony Forming Units cm−3 ( CFU cm−3 ) led to significantly reduced concentrations of ethanol and secondary metabolites in beer. The temperature decrease from 10 °C to 7 °C at pitching rate of 107 CFU cm−3 resulted in a decrease in the alcohol concentration and increase in all the secondary metabolite concentrations except for the vicinal diketones concentration. Data show that yeast biomass does not grow at 5 °C and at inoculum concentration of 107 CFU cm−3, which makes fermentation impossible. Fermentation kinetics using Monod's model supplemented with product inhibition was also investigated. Up to 1.7 % of alcohol accumulates in the beer in some of the variants within 7 days. At low fermentation temperatures, yeast biomass utilizes part of the substrate to maintain its vital activity under stress fermentation conditions, which leads to a reduction in the amount of alcohol synthesized. The synthesis and reduction of the secondary metabolites was delayed compared to conventional beer fermentation. The sensory evaluation of the beers produced showed that the most appealing beer was the one produced at 10 °C and pitching rate of 109 CFU cm−3.

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Verhagen, Frank J. M., Henk J. Swarts, Joannes B. P. A. Wijnberg et Jim A. Field. « Biotransformation of the Major Fungal Metabolite 3,5-Dichloro- p-Anisyl Alcohol under Anaerobic Conditions and Its Role in Formation of Bis(3,5-Dichloro-4-Hydroxyphenyl)methane ». Applied and Environmental Microbiology 64, n^o 9 (1 septembre 1998) : 3225–31. http://dx.doi.org/10.1128/aem.64.9.3225-3231.1998.

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ABSTRACT Higher fungi have a widespread capacity for biosynthesis of organohalogens. Commonly occurring chloroaromatic fungal metabolites can end up in anaerobic microniches at the boundary of fungal colonies and wetland soils. The aim of this study was to investigate the environmental fate of a major fungal metabolite, 3,5-dichloro-p-anisyl alcohol, under anaerobic conditions. This compound was incubated with methanogenic sludge to study its biotransformation reactions. Initially, 3,5-dichloro-p-anisyl alcohol was readily demethylated in stoichiometric quantities to 3,5-dichloro-4-hydroxybenzyl alcohol. The demethylated product was converted further via two routes: a biotic route leading to the formation of 3,5-dichloro-4-hydroxybenzoate and 2,6-dichlorophenol, as well as an abiotic route leading to the formation of bis(3,5-dichloro-4-hydroxyphenyl)methane. In the first route, the benzyl alcohol moiety on the aromatic ring was oxidized, giving 3,5-dichloro-4-hydroxybenzoate as a transient or accumulating product, depending on the type of methanogenic sludge used. In sludge previously adapted to low-molecular-weight lignin from straw, a part of the 3,5-dichloro-4-hydroxybenzoate was decarboxylated, yielding detectable levels of 2,6-dichlorophenol. In the second route, 3,5-dichloro-4-hydroxybenzyl alcohol dimerized, leading to the formation of a tetrachlorinated bisphenolic compound, which was identified as bis(3,5-dichloro-4-hydroxyphenyl)methane. Since formation of this dimer was also observed in incubations with autoclaved sludge spiked with 3,5-dichloro-4-hydroxybenzyl alcohol, it was concluded that its formation was due to an abiotic process. However, demethylation of the fungal metabolite by biological processes was a prerequisite for dimerization. The most probable reaction mechanism leading to the formation of the tetrachlorinated dimer in the absence of oxygen is presented, and the possible environmental implications of its natural occurrence are discussed.

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Urquhart, JL, et HR Goez. « P.072 Fetal alcohol spectrum disorder - is this a ciliopathy ? » Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 46, s1 (juin 2019) : S33—S34. http://dx.doi.org/10.1017/cjn.2019.172.

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Background: Fetal alcohol spectrum disorder (FASD) is used to describe the spectrum of birth defects due to prenatal alcohol exposure; these include craniofacial abnormalities and intellectual disabilities. The prevalence of FASD is estimated at 1 in 100. Diagnostic criteria include distinct facial features, neurodevelopmental deficits and confirmation of alcohol use during pregnancy. Unfortunately, often criteria are missed or absent. No biochemical marker is available for screening and diagnosis of FASD that is easy, accurate and cost-effective. Methods: Five children are being recruited from both the FASD clinic at the Glenrose Rehabilitation Hospital and the Healthy Infants and Children’s Clinical Research Program (HICUPP) registry. The levels of exhaled nasal NO will be measured and compared between the two groups. Metabolomics analysis on urine samples targeting metabolites of the NO pathway, along with other urinary metabolites is being performed. Bioinformatic statistical tools will be applied to determine whether measured metabolite profiles can provide distinct signatures between healthy children and children with FASD. Results: This project is ongoing. Conclusions: We hope to correlate NO levels with FASD, illustrating the relationship between NO, ciliopathies and development of FASD. As well, we hope to determine whether urinary metabolites may yield diagnostic markers of FASD.

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MOSKALEVA, Natalia E., Roman M. KUZNETZOV, Pavel A. MARKIN et Svetlana A. APPOLONOVA. « MASS SPECTROMETRIC CHARACTERIZATION OF PLASMA MEBEVERINE METABOLITES AND ITS SYNTHESIS ». Periódico Tchê Química 16, n^o 32 (20 août 2019) : 633–46. http://dx.doi.org/10.52571/ptq.v16.n32.2019.651_periodico32_pgs_633_646.pdf.

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Mebeverine is a musculotropic antispasmodic drug that is widely used in the treatment of irritable bowel syndrome. As an ester of mebeverine alcohol and veratric acid, mebeverin is quickly metabolized and is practically undetectable in blood plasma. The main goal of this work was establishing the structure of the main metabolites of mebeverin in human blood plasma. The study was conducted by time-of-flight mass spectrometry (LC-IT-TOF MS), metabolites of mebeverine were extracted from plasma with acetonitrile. When comparing chromatograms of blood plasma obtained before and after drug administration, four main peaks of metabolites were detected. To establish the structure of the compounds, mass spectra of the first and second order were taken. The first-order spectra were used to calculate the metabolite formula and the structure was determined from the fragmentation spectra, as well as by comparing the fragmentation spectra of mebeverine and its proposed metabolites. The proposed compounds were synthesized, and their structure was confirmed using NMR and chromatography-mass spectrometry. Four main metabolites were found in this study: desmethylmebeverine acid (DMAC), glucuronide product of DMAC (DMAC-Glu), mebeverine acid (MAC) and mebeverine alcohol (MAL). The results complement the available literature data about the veratric acid metabolism, urine, and microsomal studies. According to the data obtained, the main metabolite of mebeverine in the blood is DMAC. The concentration of MAC after mebeverine administration is almost ten times less than DMAC, the content of MAL and DMAC-Glu is insignificant, and probably does not affect the pharmacological effect of mebeverine. Therefore, the concentration of DMAC is the main parameter to be monitored in pharmacokinetics studies.

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Farkas, Á., et L. Kemény. « The alcohol metabolite acetaldehyde and psoriasis : another trigger factor ? » Clinical and Experimental Dermatology 35, n^o 8 (25 mai 2010) : 923–25. http://dx.doi.org/10.1111/j.1365-2230.2010.03866.x.

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Dorgan, Joanne F., Seungyoun Jung, Cher M. Dallal, Min Zhan, Christina A. Stennett, Yuji Zhang, Richard L. Eckert, Linda G. Snetselaar et Linda Van Horn. « Alcohol consumption and serum metabolite concentrations in young women ». Cancer Causes & ; Control 31, n^o 2 (11 décembre 2019) : 113–26. http://dx.doi.org/10.1007/s10552-019-01256-1.

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Lien, E. A., P. M. Ueland, E. Solheim et S. Kvinnsland. « Determination of tamoxifen and four metabolites in serum by low-dispersion liquid chromatography. » Clinical Chemistry 33, n^o 9 (1 septembre 1987) : 1608–14. http://dx.doi.org/10.1093/clinchem/33.9.1608.

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Abstract In this assay of tamoxifen and four metabolites in human serum, the serum samples are deproteinized with an equal volume of acetonitrile, then injected into a small (0.21 X 2 cm) precolumn packed with 5-micron-diameter octadecylsilane (ODS) particles. The samples are concentrated on-column by equilibrating the column with an equivolume solution of water and acetonitrile containing 3 mmol of acetic acid and 2 mmol of diethylamine per liter. The drugs are then directed into an analytical ODS column (0.21 X 10 cm) by changing the mobile phase followed by column switching. The primary alcohol of tamoxifen ("metabolite Y"), 4-hydroxytamoxifen ("metabolite B"), tamoxifen, N-desdimethyltamoxifen ("metabolite Z"), N-desmethyltamoxifen ("metabolite X"), and 4-methoxytamoxifen (internal standard) are eluted in this order at a flow rate of 0.3 mL/min with a mobile phase of acetonitrile/water (91/9 by vol) at low ionic strength (1 mmol of acetic acid and 0.67 mmol of diethylamine per liter) and detected by post-column fluorescence activation by passage through a capillary quartz tube exposed to ultraviolet light. Analytical recovery was close to 100%. Within-day precision corresponded to a CV of 1-5% at serum concentrations of tamoxifen or metabolites greater than 10 micrograms/L; the detection limit of the assay for these compounds was about 1 microgram/L. This fully automated assay has the advantage of simple sample processing, high sample output, low solvent consumption, high analytical recovery of tamoxifen and four metabolites in serum, and determination of all these compounds plus an internal standard in a single run.

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Chak, Choiwai, Maria Lacruz, Jonathan Adam, Stefan Brandmaier, Marcela Covic, Jialing Huang, Christa Meisinger et al. « Ageing Investigation Using Two-Time-Point Metabolomics Data from KORA and CARLA Studies ». Metabolites 9, n^o 3 (5 mars 2019) : 44. http://dx.doi.org/10.3390/metabo9030044.

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Ageing, one of the largest risk factors for many complex diseases, is highly interconnected to metabolic processes. Investigating the changes in metabolite concentration during ageing among healthy individuals offers us unique insights to healthy ageing. We aim to identify ageing-associated metabolites that are independent from chronological age to deepen our understanding of the long-term changes in metabolites upon ageing. Sex-stratified longitudinal analyses were performed using fasting serum samples of 590 healthy KORA individuals (317 women and 273 men) who participated in both baseline (KORA S4) and seven-year follow-up (KORA F4) studies. Replication was conducted using serum samples of 386 healthy CARLA participants (195 women and 191 men) in both baseline (CARLA-0) and four-year follow-up (CARLA-1) studies. Generalized estimation equation models were performed on each metabolite to identify ageing-associated metabolites after adjusting for baseline chronological age, body mass index, physical activity, smoking status, alcohol intake and systolic blood pressure. Literature researches were conducted to understand their biochemical relevance. Out of 122 metabolites analysed, we identified and replicated five (C18, arginine, ornithine, serine and tyrosine) and four (arginine, ornithine, PC aa C36:3 and PC ae C40:5) significant metabolites in women and men respectively. Arginine decreased, while ornithine increased in both sexes. These metabolites are involved in several ageing processes: apoptosis, mitochondrial dysfunction, inflammation, lipid metabolism, autophagy and oxidative stress resistance. The study reveals several significant ageing-associated metabolite changes with two-time-point measurements on healthy individuals. Larger studies are required to confirm our findings.

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Brudea, V., I. Rîşca, C. Enea et C. Tomescu. « Efficacy of Some Biopesticides and Plant Secondary Metabolites Against Fall Webworm Hyphantria Cunea Drury (F. Arctiidae-Lepidoptera) in the Lab Conditions ». Cercetari Agronomice in Moldova 45, n^o 1 (1 janvier 2012) : 73–80. http://dx.doi.org/10.2478/v10298-012-0007-8.

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Efficacy of Some Biopesticides and Plant Secondary Metabolites Against Fall Webworm Hyphantria Cunea Drury (F. Arctiidae-Lepidoptera) in the Lab Conditions The paper presents the efficacy of the some biopesticides used in the experiments to control fall webworm (Hyphantria cunea), comparatively to some plant secondary metabolites from autochthonous flora. From the first category there were used: spinosad, a secondary metabolite produces by the fermentation from Saccharopolyspora spinosa mushroom and is the active principle of the commercial products of the Naturalyte class; azadyrachtines - a group of limonoids, obtained from the seeds of the Neem tree (Azadirachta indica), and milbecmectin, a product obtained from a metabolite of the Streptomyces hygroscopicus subsp. aureolacrimans bacteria. The results revealed the efficacy of all bio insecticides against fall webworm in 2-7 days period after treatment. Spinosad presented a quick action, comparatively to the other bio pesticides. The secondary metabolites, used into fall webworm control, were extracted from autochthonous plants: the common ladyfern (Drioperis filix mas), the perennial sage (Salvia nemorosa), the wormwood (Artemisia dracunculus, A. vulgaris, A. absinthium) the European birthwort (Aristolochia clematidis), Cow parsnip (Heracleum spondylium), the hedge nettle (Stachis sylvatica), the speedwell (Tanacetum vulgare), the nettle (Urtica dioica), the danewort (Sambucus ebulus) and the yew tree (Taxus baccata) to fall webworm. Plants extracts were obtained from dried ground plants, using 25 g/ 1 litter of cold water, stirred for 24 hours. The extracts in ethylic alcohol were made using the same method, 25 g dried plants in 200 ml alcohol and completed up to 1 litter with water. The experiments were carried out under laboratory conditions, treatments being applied on shoots with leaves affected by fall webworm, placed in growth boxes. Each variant had three replications and each replication contained three infested shoots. The treatments were applied with manual small pumps. Efficacy (E%) was calculated after Săvescu-Iacob formula. The majority of alcoholic plant extracts influenced the decrease of leafs consumption as extracts with water. Extracts of metabolites influenced the eating with repellent effects against larvae, no palatable etc. The future experiments must use more chemical analyses to discriminate the main metabolites, which influence the worm activities.

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Anderson, Chelsea, Ginger L. Milne, Dale P. Sandler et Hazel B. Nichols. « Oxidative stress in relation to diet and physical activity among premenopausal women ». British Journal of Nutrition 116, n^o 8 (11 octobre 2016) : 1416–24. http://dx.doi.org/10.1017/s0007114516003226.

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AbstractHigher levels of oxidative stress, as measured by F2-isoprostanes, have been associated with chronic diseases such as CVD and some cancers. Improvements in diet and physical activity may help reduce oxidative stress; however, previous studies regarding associations between lifestyle factors and F2-isoprostane concentrations have been inconsistent. The aim of this cross-sectional study was to investigate whether physical activity and intakes of fruits/vegetables, antioxidant nutrients, dietary fat subgroups and alcohol are associated with concentrations of F2-isoprostane and the major F2-isoprostane metabolite. Urinary F2-isoprostane and its metabolite were measured in urine samples collected at enrolment from 912 premenopausal women (aged 35–54 years) participating in the Sister Study. Physical activity, alcohol consumption and dietary intakes were self-reported via questionnaires. With adjustment for potential confounders, the geometric means of F2-isoprostane and its metabolite were calculated according to quartiles of dietary intakes, alcohol consumption and physical activity, and linear regression models were used to evaluate trends. Significant inverse associations were found between F2-isoprostane and/or its metabolite and physical activity, vegetables, fruits, vitamin C, α-carotene, vitamin E, β-carotene, vitamin A, Se, lutein+zeaxanthin and long-chain n-3 fatty acids. Although trans fats were positively associated with both F2-isoprostane and its metabolite, other dietary fat subgroups including SFA, n-6 fatty acids, n-3 fatty acids, MUFA, PUFA, short-chain n-3 fatty acids, long-chain n-3 fatty acids and total fat were not associated with either F2-isoprostane or its metabolite. Our findings suggest that lower intake of antioxidant nutrients and higher intake of trans fats may be associated with greater oxidative stress among premenopausal women.

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Li, Shumei, Xueqiang Su, Muhammad Abdullah, Yanming Sun, Guohui Li, Xi Cheng, Yi Lin, Yongping Cai et Qing Jin. « Effects of Different Pollens on Primary Metabolism and Lignin Biosynthesis in Pear ». International Journal of Molecular Sciences 19, n^o 8 (2 août 2018) : 2273. http://dx.doi.org/10.3390/ijms19082273.

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To investigate the effect of pollination on the fruit quality of ‘Dangshan Su’ pear, ‘Dangshan Su’ was fertilized by the pollen of ‘Wonhwang’ (Pyrus pyrifolia Nakai.) (DW) and ‘Jingbaili’ (Pyrus ussuriensis Maxim.) (DJ). The analysis of primary metabolites was achieved through untargeted metabolomics, and the quantitative analysis of intermediate metabolites of lignin synthesis was undertaken using targeted metabolomics. The untargeted metabolomics analysis was performed via gas chromatography-mass spectrometry (GC-MS). The targeted metabolomics analysis was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) under the multiple reaction monitoring (MRM) mode. The results showed that the metabolite content was significantly different between DW and DJ. Compared with that in DJ, the sugar and amino acid content in DW was higher and the fatty acid content was lower at 47 days after pollination (DAPs), and the sugar, amino acid, and fatty acid content in DW was lower at 63 DAPs. The intermediate metabolites of lignin synthesis were analyzed using the orthogonal partial least squares discriminant analysis (OPLS-DA) model, and the differential metabolites at 47 DAPs were p-coumaric acid, ferulic acid, sinapaldehyde, coniferyl alcohol, and sinapyl alcohol. The differential significant metabolite at 63 DAPs was p-coumaric acid. At 47 DAPs and 63 DAPs, the p-coumaric acid level was significantly different, and the p-coumaric acid content was positively correlated with lignin synthesis. The pollination pollen affects the quality of ‘Dangshan Su’ pear fruit through regulation of the sugar, amino acid, and fatty acid content; at the same time, regulating the levels of intermediate metabolites of lignin synthesis, especially the p-coumaric acid content, to affect lignin synthesis ultimately affects the stone cell content and improves the quality of the pears.

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Zhang, Tianlei, Aihua Zhang, Shi Qiu, Hui Sun, Ying Han, Yu Guan et Xijun Wang. « High-throughput metabolomics approach reveals new mechanistic insights for drug response of phenotypes of geniposide towards alcohol-induced liver injury by using liquid chromatography coupled to high resolution mass spectrometry ». Molecular BioSystems 13, n^o 1 (2017) : 73–82. http://dx.doi.org/10.1039/c6mb00742b.

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Zhang, Qiuping, Xiaoxue Ma, Weisheng Liu, Ning Liu, Yuping Zhang, Ming Xu, Shuo Liu, Yujun Zhang, Haijuan Zhao et Jiacheng Liu. « Metabolomics Data Revealed Metabolite Changes during Endocarp Lignification in Kernel-Using Apricot ». Horticulturae 8, n^o 10 (19 octobre 2022) : 967. http://dx.doi.org/10.3390/horticulturae8100967.

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To understand the metabolite dynamics and genetic regulatory mechanism of apricot shell, a typical endocarp, before and after lignification are unknown, we investigated the metabolite differences of the endocarp of ‘Youyi,’ a popular kernel-using apricot cultivar, using ultra-performance liquid chromatography tandem mass spectrometry strategy. The endocarp thickness increased rapidly from 8 to 37 days after flowering (DAF) and lignin deposition began at 37 DAF. In total, 626 non-volatile metabolites were obtained from the endocarp tissues before (33 DAF) and after (41 and 45 DAF) lignification. The relative sugar and organic acid contents decreased continuously and those of L-phenylalanine and L-tyrosine increased after lignification. In the non-lignified endocarp, the phenylpropanoid metabolites were mainly in the form of p-coumaric acid, ferulic acid, neochlorogenic acid, dicumarol, coniferin, and some lignans. After lignification, the metabolites were mainly in the form of glycoside lignin or lactone coumarins, and the relative contents of L-asarinin and forsythin increased. The results of transcriptome confirmed the upregulation of genes related to lignin biosynthesis, including β-glucosidase and coniferyl-alcohol glucosyltransferase and laccases, accelerated lignification. This study provides insights into the formation of lignified endocarp in a kernel-using apricot and clarifies the role of monolignin transport and oxidative polymerization.

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Barr, Christina S., Michelle L. Becker, Stephen J. Suomi et J. Dee Higley. « Relationships among CSF monoamine metabolite levels, alcohol sensitivity, and alcohol-related aggression in rhesus macaques ». Aggressive Behavior 29, n^o 4 (15 juillet 2003) : 288–301. http://dx.doi.org/10.1002/ab.10071.

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Koch, Wolf-Gerald, et Volker Sinnwell. « Isopulegol from Liquid Cultures of the Fungus Ceratocystis coerulescens (Ascomycotina) ». Zeitschrift für Naturforschung C 42, n^o 1-2 (1 février 1987) : 159–61. http://dx.doi.org/10.1515/znc-1987-1-227.

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Abstract Ceratocystis coerulescens RWD 451 (Ascomycetes) was cultivated on defined synthetic culture medium containing glucose (3.0% ), asparagine (0.1% ), mineral salts and thiamine. 6 weeks oid cultures produced methyl heptenyl compounds, citronellol. citronellyl acetate, dihydro-farnesol and a hitherto unknown monoterpene alcohol. By GC/MS, 1H and 13C NMR spectroscopy, this alcohol could be identified as ( -)isopulegol. So far, this monocyclic monoterpene alcohol has not been described as a fungal metabolite.

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Buchholz, Bruce A., Ki Chang Ahn, Huazhang Huang, Shirley J. Gee, Benjamin J. Stewart, Ted J. Ognibene et Bruce D. Hammock. « Pharmacokinetics, Metabolite Measurement, and Biomarker Identification of Dermal Exposure to Permethrin Using Accelerator Mass Spectrometry ». Toxicological Sciences 183, n^o 1 (21 juin 2021) : 49–59. http://dx.doi.org/10.1093/toxsci/kfab082.

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Abstract Impregnating military uniforms and outdoor clothing with the insecticide permethrin is an approach to reduce exposure to insect borne diseases and to repel pests and disease vectors such as mosquitos and sandflies, but the practice exposes wearers to prolonged dermal exposure to the pesticide. Key metabolite(s) from a low dose dermal exposure of permethrin were identified using accelerator mass spectrometry. Metabolite standards were synthesized and a high performance liquide chromatography (HPLC) elution protocol to separate individual metabolites in urine was developed. Six human subjects were exposed dermally on the forearm to 25 mg of permethrin containing 1.0 µCi of 14C for 8 h. Blood, saliva and urine samples were taken for 7d. Absorption/elimination rates and metabolite concentrations varied by individual. Average absorption was 0.2% of the dose. Serum concentrations rose until 12–24 h postdermal application then rapidly declined reaching predose levels by 72 h. Maximum saliva excretion occurred 6 h postdosing. The maximum urinary excretion rate occurred during 12–24 h; average elimination half-life was 56 h. 3-Phenoxybenzyl alcohol glucuronide was the most abundant metabolite identified when analyzing elution fractions, but most of the radioactivity was in still more polar fractions suggesting extensive degradative metabolism and for which there were no standards. Analyses of archived urine samples with the ultra performance liquid chromatography-accelerator mass spectrometry-mass spectrometry (UPLC-AMS-MS) system isolated a distinct polar metabolite but it was much diminished from the previous analyses a decade earlier.

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Wurst, Friedrich Martin, Sebastian Dresen, John P. Allen, Gerhard Wiesbeck, Marc Graf et Wolfgang Weinmann. « Ethyl sulphate : a direct ethanol metabolite reflecting recent alcohol consumption ». Addiction 101, n^o 2 (février 2006) : 204–11. http://dx.doi.org/10.1111/j.1360-0443.2005.01245.x.

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Landry, Mim J. « An Overview of Cocaethylene, An Alcohol-Derived, Psychoactive, Cocaine Metabolite ». Journal of Psychoactive Drugs 24, n^o 3 (juillet 1992) : 273–76. http://dx.doi.org/10.1080/02791072.1992.10471648.

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Jílek, Jiří, Jiří Holubek, Emil Svátek, Jiří Schlanger, Josef Pomykáček et Miroslav Protiva. « Highly polar potential metabolites of the neuroleptic agent oxyprothepin : Synthesis of 2-hydroxy-8-methylsulfonyl and 3-hydroxy-8-methylsulfonyl derivatives of 10-[4-(3-hydroxypropyl)piperazino]-10,11-dihydrodibenzo[b,f]thiepin ». Collection of Czechoslovak Chemical Communications 50, n^o 2 (1985) : 519–37. http://dx.doi.org/10.1135/cccc19850519.

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The acid XI, obtained by reaction of (2-iodo-5-methoxyphenyl)acetic acid with 4-(methylsulfonyl)thiophenol (VIII) in dimethylformamide in the presence of potassium carbonate and copper, was transformed via intermediates XIIa-XIVa to compound XVa. Demethylation with boron tribromide afforded compound III, the potential metabolite of oxyprothepin (II). Its oxidation with hydrogen peroxide in acetic acid gave the sulfoxide XVII, which is a further potential metabolite. A reaction of 2-iodo-4-methoxybenzoic acid with VIII and potassium carbonate in dimethylformamide in the presence of copper afforded the acid XIX whose ester XXI was reduced with diborane to the alcohol XXII; hydrogenolysis to compound XXIII was also observed. The alcohol XXII was processed via compounds XXIV and XXV to the acid XXVI which was cyclized in a low yield to the ketone XIIb. A further processing via the intermediates XIIIb and XIVb led to compound XVb. Demethylation gave compound IV, another potential metabolite.

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T. Gailliot, Matthew. « Alcohol Consumption Reduces Effortful Fatigue After Sleep : Testing A Theory of Metabolite Depletion and Subsequent Supercompensation ». JOURNAL OF ADVANCES IN HUMANITIES 3, n^o 3 (25 décembre 2015) : 271–76. http://dx.doi.org/10.24297/jah.v3i2.5140.

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The current work examined whether greater alcohol consumption at night would predict less effortful fatigue the next morning. The theory is that effortful thought and behavior benefit from additional stored metabolites, and that drinking alcohol temporarily reduces metabolites but later increases them. Participants attended a drinking, social event at night. The next morning, they completed an effortful task (a breath-blowing task requiring forceful exertion and persistence) before and after a mentally fatiguing task (controlling attention). Consuming more alcohol during the event predicted less fatigue on the effortful breath-blowing task, computed as the difference between performance on the task before and after the attention control task. Alcohol consumption might be one strategy for reducing later fatigue on effortful tasks.

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Opitz, Antje, Jan Hubert, Christian Beste et Ann-Kathrin Stock. « Alcohol Hangover Slightly Impairs Response Selection but not Response Inhibition ». Journal of Clinical Medicine 8, n^o 9 (27 août 2019) : 1317. http://dx.doi.org/10.3390/jcm8091317.

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Alcohol hangover commonly occurs after an episode of heavy drinking. It has previously been demonstrated that acute high-dose alcohol intoxication reduces cognitive control, while automatic processes remain comparatively unaffected. However, it has remained unclear whether alcohol hangover, as a consequence of binge drinking, modulates the interplay between cognitive control and automaticity in a comparable way. Therefore, the purpose of this study was to investigate the effects of alcohol hangover on controlled versus automatic response selection and inhibition. N = 34 healthy young men completed a Simon Nogo task, once sober and once hungover. Hangover symptoms were experimentally induced by a standardized administration of alcoholic drinks (with high congener content) on the night before the hangover appointment. We found no significant hangover effects, which suggests that alcohol hangover did not produce the same functional deficits as an acute high-dose intoxication. Yet still, add-on Bayesian analyses revealed that hangover slightly impaired response selection, but not response inhibition. This pattern of effects cannot be explained with the current knowledge on how ethanol and its metabolite acetaldehyde may modulate response selection and inhibition via the dopaminergic or GABAergic system.

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Kiran, Ismail. « Microbial Hydroxylation of S-(-)-Perillyl Alcohol by Fusarium heterosporium ». Natural Product Communications 6, n^o 12 (décembre 2011) : 1934578X1100601. http://dx.doi.org/10.1177/1934578x1100601203.

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S-(-)-Perillyl alcohol ( p-mentha-1, 8-diene-7-ol) (1) (500 mg) was converted by Fusarium heterosporium ATCC 15625 over 10 days at 25°C to a new metabolite, 1,2-dihydroxyperillyl alcohol ( p-mentha-8-en-1,2,7-triol) (3) in a yield of 13% (70 mg). The structure of 3 was established by IR and NMR spectroscopic, specific rotation, and mass spectral studies.

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Dahal, Sanjeev, Gregory B. Hurst, Karuna Chourey, Nancy L. Engle, Leah H. Burdick, Jennifer L. Morrell-Falvey, Timothy J. Tschaplinski, Mitchel J. Doktycz et Dale A. Pelletier. « Mechanism for Utilization of the Populus-Derived Metabolite Salicin by a Pseudomonas—Rahnella Co-Culture ». Metabolites 13, n^o 2 (17 janvier 2023) : 140. http://dx.doi.org/10.3390/metabo13020140.

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Pseudomonas fluorescens GM16 associates with Populus, a model plant in biofuel production. Populus releases abundant phenolic glycosides such as salicin, but P. fluorescens GM16 cannot utilize salicin, whereas Pseudomonas strains are known to utilize compounds similar to the aglycone moiety of salicin–salicyl alcohol. We propose that the association of Pseudomonas to Populus is mediated by another organism (such as Rahnella aquatilis OV744) that degrades the glucosyl group of salicin. In this study, we demonstrate that in the Rahnella–Pseudomonas salicin co-culture model, Rahnella grows by degrading salicin to glucose 6-phosphate and salicyl alcohol which is secreted out and is subsequently utilized by P. fluorescens GM16 for its growth. Using various quantitative approaches, we elucidate the individual pathways for salicin and salicyl alcohol metabolism present in Rahnella and Pseudomonas, respectively. Furthermore, we were able to establish that the salicyl alcohol cross-feeding interaction between the two strains on salicin medium is carried out through the combination of their respective individual pathways. The research presents one of the potential advantages of salicyl alcohol release by strains such as Rahnella, and how phenolic glycosides could be involved in attracting multiple types of bacteria into the Populus microbiome.

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Lindsay, Melodie A., Ninna Granucci, David R. Greenwood et Silas G. Villas-Boas. « Fermentative Production of Volatile Metabolites Using Brettanomyces bruxellensis from Fruit and Vegetable By-Products ». Fermentation 8, n^o 9 (12 septembre 2022) : 457. http://dx.doi.org/10.3390/fermentation8090457.

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Natural sources of flavour and aroma compounds are highly sought by the modern consumer; however, traditional sources are often low-yielding, and global supply is often outstripped by consumer demand. Fermentation is a favourable route by which natural flavours and fragrances can be produced. A non-Saccharomyces yeast, Brettanomyces bruxellensis, was investigated for its fermentative potential for the production of flavour and aroma metabolites from juice industry by-products: apple pomace, carrot pomace, and orange pomace. Submerged solid-substrate fermentations were carried out using sterile by-products without nutrient supplementation. Gas chromatography–mass spectrometry was used for volatile metabolite profiling of fermented substrates. One compound of interest, phenylethyl alcohol (rose fragrance), was extracted and quantified using GC-MS at a yield of 2.68 g/kg wet carrot pomace weight. This represents a novel, natural production strategy for phenylethyl alcohol compared to the traditional steam distillation of Rosa domascus sp. petals.

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Setshedi, Mashiko, Jack R. Wands et Suzanne M. de la Monte. « Acetaldehyde Adducts in Alcoholic Liver Disease ». Oxidative Medicine and Cellular Longevity 3, n^o 3 (2010) : 178–85. http://dx.doi.org/10.4161/oxim.3.3.12288.

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Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD), with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC). Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15%) versus cirrhosis (15–20%) is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

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Niemelä, Onni, Anni Halkola, Aini Bloigu, Risto Bloigu, Ulla Nivukoski, Heidi Pohjasniemi et Johanna Kultti. « Blood Cell Responses Following Heavy Alcohol Consumption Coincide with Changes in Acute Phase Reactants of Inflammation, Indices of Hemolysis and Immune Responses to Ethanol Metabolites ». International Journal of Molecular Sciences 23, n^o 21 (22 octobre 2022) : 12738. http://dx.doi.org/10.3390/ijms232112738.

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Aberrations in blood cells are common among heavy alcohol drinkers. In order to shed further light on such responses, we compared blood cell status with markers of hemolysis, mediators of inflammation and immune responses to ethanol metabolites in alcohol-dependent patients at the time of admission for detoxification and after abstinence. Blood cell counts, indices of hemolysis (LDH, haptoglobin, bilirubin), calprotectin (a marker of neutrophil activation), suPAR, CD163, pro- and anti-inflammatory cytokines and autoantibodies against protein adducts with acetaldehyde, the first metabolite of ethanol, were measured from alcohol-dependent patients (73 men, 26 women, mean age 43.8 ± 10.4 years) at baseline and after 8 ± 1 days of abstinence. The assessments also included information on the quantities of alcohol drinking and assays for biomarkers of alcohol consumption (CDT), liver function (AST, ALT, ALP, GGT) and acute phase reactants of inflammation. At baseline, the patients showed elevated values of CDT and biomarkers of liver status, which decreased significantly during abstinence. A significant decrease also occurred in LDH, bilirubin, CD163 and IgA and IgM antibodies against acetaldehyde adducts, whereas a significant increase was noted in blood leukocytes, platelets, MCV and suPAR levels. The changes in blood leukocytes correlated with those in serum calprotectin (p < 0.001), haptoglobin (p < 0.001), IL-6 (p < 0.02) and suPAR (p < 0.02). The changes in MCV correlated with those in LDH (p < 0.02), MCH (p < 0.01), bilirubin (p < 0.001) and anti-adduct IgG (p < 0.01). The data indicates that ethanol-induced changes in blood leukocytes are related with acute phase reactants of inflammation and release of neutrophil calprotectin. The studies also highlight the role of hemolysis and immune responses to ethanol metabolites underlying erythrocyte abnormalities in alcohol abusers.

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Niemelä, Onni, Anni Halkola, Aini Bloigu, Risto Bloigu, Ulla Nivukoski, Heidi Pohjasniemi et Johanna Kultti. « Blood Cell Responses Following Heavy Alcohol Consumption Coincide with Changes in Acute Phase Reactants of Inflammation, Indices of Hemolysis and Immune Responses to Ethanol Metabolites ». International Journal of Molecular Sciences 23, n^o 21 (22 octobre 2022) : 12738. http://dx.doi.org/10.3390/ijms232112738.

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Aberrations in blood cells are common among heavy alcohol drinkers. In order to shed further light on such responses, we compared blood cell status with markers of hemolysis, mediators of inflammation and immune responses to ethanol metabolites in alcohol-dependent patients at the time of admission for detoxification and after abstinence. Blood cell counts, indices of hemolysis (LDH, haptoglobin, bilirubin), calprotectin (a marker of neutrophil activation), suPAR, CD163, pro- and anti-inflammatory cytokines and autoantibodies against protein adducts with acetaldehyde, the first metabolite of ethanol, were measured from alcohol-dependent patients (73 men, 26 women, mean age 43.8 ± 10.4 years) at baseline and after 8 ± 1 days of abstinence. The assessments also included information on the quantities of alcohol drinking and assays for biomarkers of alcohol consumption (CDT), liver function (AST, ALT, ALP, GGT) and acute phase reactants of inflammation. At baseline, the patients showed elevated values of CDT and biomarkers of liver status, which decreased significantly during abstinence. A significant decrease also occurred in LDH, bilirubin, CD163 and IgA and IgM antibodies against acetaldehyde adducts, whereas a significant increase was noted in blood leukocytes, platelets, MCV and suPAR levels. The changes in blood leukocytes correlated with those in serum calprotectin (p < 0.001), haptoglobin (p < 0.001), IL-6 (p < 0.02) and suPAR (p < 0.02). The changes in MCV correlated with those in LDH (p < 0.02), MCH (p < 0.01), bilirubin (p < 0.001) and anti-adduct IgG (p < 0.01). The data indicates that ethanol-induced changes in blood leukocytes are related with acute phase reactants of inflammation and release of neutrophil calprotectin. The studies also highlight the role of hemolysis and immune responses to ethanol metabolites underlying erythrocyte abnormalities in alcohol abusers.

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