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Drug Metabolism Reviews Nov 2019This article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on... (Review)
Review
This article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on their immunomodulatory effects. The section dealing with the toxic effects of alcohol focuses on its chronic toxicity (liver disorders, carcinogenic effects, cardiovascular disorders, neuropsychic disorders, addiction and withdrawal syndrome, hematologic disorders, reprotoxicity, osteoporosis) although acute toxicity is considered. The role of oxidative metabolism of ethanol by alcohol dehydrogenase, cytochrome P450 2E1, and aldehyde dehydrogenase, as well as the impact of genetic polymorphism in its physiopathology are also highlighted. The section dealing with the beneficial effects of low to moderate alcohol consumption (on cardiovascular system, diabetes, the nervous system and sensory organs, autoimmune diseases, and rheumatology) highlights the importance of anti-inflammatory and immunomodulatory effects in these observations. This knowledge, enriched by a focus on the immunomodulatory effects of ethanol and its metabolites, in particular on the NLRP3 inflammasome pathway, might facilitate the development of treatments that can reduce ethanol's harmful effects or accentuate its beneficial effects.
Topics: Alcohol Drinking; Alcoholism; Animals; Ethanol; Humans; Immunologic Factors
PubMed: 31646907
DOI: 10.1080/03602532.2019.1679169 -
Nutrients Sep 2021Approximately 4% of cancers worldwide are caused by alcohol consumption. Drinking alcohol increases the risk of several cancer types, including cancers of the upper... (Review)
Review
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.
Topics: Acetaldehyde; Alcohol Drinking; Alcohol-Induced Disorders; Carcinogenesis; DNA Damage; DNA Methylation; Ethanol; Humans; Neoplasms
PubMed: 34579050
DOI: 10.3390/nu13093173 -
Trends in Neurosciences Dec 2021Alcohol use produces wide-ranging and diverse effects on the central nervous system. It influences intracellular signaling mechanisms, leading to changes in gene... (Review)
Review
Alcohol use produces wide-ranging and diverse effects on the central nervous system. It influences intracellular signaling mechanisms, leading to changes in gene expression, chromatin remodeling, and translation. As a result of these molecular alterations, alcohol affects the activity of neuronal circuits. Together, these mechanisms produce long-lasting cellular adaptations in the brain that in turn can drive the development and maintenance of alcohol use disorder (AUD). We provide an update on alcohol research, focusing on multiple levels of alcohol-induced adaptations, from intracellular changes to changes in neural circuits. A better understanding of how alcohol affects these diverse and interlinked mechanisms may lead to the identification of novel therapeutic targets and to the development of much-needed novel and efficacious treatment options.
Topics: Alcoholism; Brain; Chromatin Assembly and Disassembly; Ethanol; Humans; Neurons
PubMed: 34702580
DOI: 10.1016/j.tins.2021.09.006 -
Alcohol Health and Research World 1998A plethora of hormones regulate many of the body's functions, including growth and development, metabolism, electrolyte balances, and reproduction. Numerous glands... (Review)
Review
A plethora of hormones regulate many of the body's functions, including growth and development, metabolism, electrolyte balances, and reproduction. Numerous glands throughout the body produce hormones. The hypothalamus produces several releasing and inhibiting hormones that act on the pituitary gland, stimulating the release of pituitary hormones. Of the pituitary hormones, several act on other glands located in various regions of the body, whereas other pituitary hormones directly affect their target organs. Other hormone-producing glands throughout the body include the adrenal glands, which primarily produce cortisol; the gonads (i.e., ovaries and testes), which produce sex hormones; the thyroid, which produces thyroid hormone; the parathyroid, which produces parathyroid hormone; and the pancreas, which produces insulin and glucagon. Many of these hormones are part of regulatory hormonal cascades involving a hypothalamic hormone, one or more pituitary hormones, and one or more target gland hormones.
Topics: Endocrine Glands; Ethanol; Hormones; Humans
PubMed: 15706790
DOI: No ID Found -
Neuron Dec 2017Ethanol is one of the most commonly abused drugs. Although environmental and genetic factors contribute to the etiology of alcohol use disorders, it is ethanol's actions... (Review)
Review
Ethanol is one of the most commonly abused drugs. Although environmental and genetic factors contribute to the etiology of alcohol use disorders, it is ethanol's actions in the brain that explain (1) acute ethanol-related behavioral changes, such as stimulant followed by depressant effects, and (2) chronic changes in behavior, including escalated use, tolerance, compulsive seeking, and dependence. Our knowledge of ethanol use and abuse thus relies on understanding its effects on the brain. Scientists have employed both bottom-up and top-down approaches, building from molecular targets to behavioral analyses and vice versa, respectively. This review highlights current progress in the field, focusing on recent and emerging molecular, cellular, and circuit effects of the drug that impact ethanol-related behaviors. The focus of the field is now on pinpointing which molecular effects in specific neurons within a brain region contribute to behavioral changes across the course of acute and chronic ethanol exposure.
Topics: Alcoholism; Animals; Brain; Ethanol; Humans; Nerve Net; Neuronal Plasticity; Neurons
PubMed: 29268093
DOI: 10.1016/j.neuron.2017.10.032 -
Nutrients Mar 2020The effects of alcohol on cardiovascular health are heterogeneous and vary according toconsumption dose and pattern. These effects have classically been described as... (Review)
Review
The effects of alcohol on cardiovascular health are heterogeneous and vary according toconsumption dose and pattern. These effects have classically been described as having a J-shapedcurve, in which low-to-moderate consumption is associated with less risk than lifetime abstention,and heavy drinkers show the highest risk. Nonetheless, the beneficial effects of alcohol have beenquestioned due to the difficulties in establishing a safe drinking threshold. This review focuses onthe association between alcohol consumption and cardiovascular risk factors and the underlyingmechanisms of damage, with review of the literature from the last 10 years.
Topics: Alcohol Drinking; Cardiovascular Diseases; Cardiovascular System; Diabetes Mellitus, Type 2; Ethanol; Humans; Inflammation; Oxidative Stress; Risk Factors
PubMed: 32230720
DOI: 10.3390/nu12040912 -
Nutrients Mar 2023Chronic alcohol use has been attributed to the development of malnutrition. This is in part due to the inhibitory effect of ethanol on the absorption of vital nutrients,... (Review)
Review
Chronic alcohol use has been attributed to the development of malnutrition. This is in part due to the inhibitory effect of ethanol on the absorption of vital nutrients, including glucose, amino acids, lipids, water, vitamins, and minerals within the small intestine. Recent advances in research, along with new cutting-edge technologies, have advanced our understanding of the mechanism of ethanol's effect on intestinal nutrient absorption at the brush border membrane (BBM) of the small intestine. However, further studies are needed to delineate how ethanol consumption could have an impact on altered nutrient absorption under various disease conditions. Current research has elucidated the relationship of alcohol consumption on glucose, glutamine, vitamins B1 (thiamine), B2 (riboflavin), B9 (folate), C (ascorbic acid), selenium, iron, and zinc absorption within the small intestine. We conducted systematic computerized searches in PubMed using the following keywords: (1) "Alcohol effects on nutrient transport"; (2) "Alcohol mediated malabsorption of nutrients"; (3) "Alcohol effects on small intestinal nutrient transport"; and (4) "Alcohol mediated malabsorption of nutrients in small intestine". We included the relevant studies in this review. The main objective of this review is to marshal and analyze previously published research articles and discuss, in-depth, the understanding of ethanol's effect in modulating absorption of vital macro and micronutrients in health and disease conditions. This could ultimately provide great insights in the development of new therapeutic strategies to combat malnutrition associated with alcohol consumption.
Topics: Humans; Intestinal Absorption; Alcohol Drinking; Ethanol; Nutrients; Malnutrition; Vitamins; Glucose
PubMed: 37049411
DOI: 10.3390/nu15071571 -
United European Gastroenterology Journal Apr 2021The gut fermentation syndrome (GFS), also known as the endogenous alcohol fermentation syndrome or auto brewery syndrome, is a rare and underdiagnosed medical condition...
BACKGROUND
The gut fermentation syndrome (GFS), also known as the endogenous alcohol fermentation syndrome or auto brewery syndrome, is a rare and underdiagnosed medical condition where consumed carbohydrates are converted to alcohol by the microbiota in the gastrointestinal or urinary tract. The symptoms of GFS can have severe impact on patients' wellbeing and can have social and legal consequences. Unfortunately, not much is reported about GFS. The aim of this systematic review was to assess the evidence for GFS, causal micro-organisms, diagnostics, and possible treatments.
METHODS
A protocol was developed prior to initiation of the systematic review (PROSPERO 207182). We performed a literature search for clinical studies on 1 September 2020 using PubMed and Embase. We included all clinical studies, including case reports that described the GFS.
RESULTS
In total, 17 case reports were included, consisting of 20 patients diagnosed with GFS. The species that caused the GFS included Klebsiella pneumoniae, Candida albicans, C. glabrata, Saccharomyces cerevisiae, C. intermedia, C. parapsilosis, and C. kefyr.
CONCLUSIONS
GFS is a rare but underdiagnosed disease in daily practice. The disease is mostly reported by Saccharomyces and Candida genera, and some cases were previously treated with antibiotics. Studies in Nonalcoholic Fatty Liver disease suggest a bacterial origin of endogenous alcohol-production, which might also be causal micro-organisms in GFS. Current treatments for GFS include antibiotics, antifungal medication, low carbohydrate diet, and probiotics. There might be a potential role of fecal microbiota transplant in the treatment of GFS.
Topics: Anti-Bacterial Agents; Antifungal Agents; Bias; Candida; Diet, Carbohydrate-Restricted; Dietary Carbohydrates; Ethanol; Fecal Microbiota Transplantation; Fermentation; Gastrointestinal Microbiome; Humans; Klebsiella pneumoniae; Medical Records; Non-alcoholic Fatty Liver Disease; Probiotics; Saccharomyces cerevisiae; Syndrome
PubMed: 33887125
DOI: 10.1002/ueg2.12062 -
Alcoholism, Clinical and Experimental... Jul 2008The development of a relatively simple, noninvasive method for estimating blood ethanol concentrations in mice will be useful in behavioral studies related to...
BACKGROUND
The development of a relatively simple, noninvasive method for estimating blood ethanol concentrations in mice will be useful in behavioral studies related to alcoholism. This study validated such a method.
METHODS
The apparatus consists of a body chamber fitted with a head stock through which the mouse head protrudes. This was fitted against a water-jacketed head-space chamber surrounding the mouse's head. Rebreathed air maintained at 37 degrees C in the head-space chamber was removed using a peristaltic pump and loaded into a 1-ml injection loop. Ethanol in the sample was quantified using gas chromatography. To validate this method, ethanol levels in breath samples were compared against those in tail blood samples collected immediately after the breath samples. Breath samples were collected at 5, 10, 20, 40, 80, 120, and 160 minutes after ethanol (0.4, 0.8, 1.2, 1.6, 2.4, and 3.2 g/kg) was administered to male C57BL/6J mice.
RESULTS
Breath and blood ethanol levels were well correlated (r(2) = 0.96) across time points on the descending ethanol-time curve at doses below 2.4 g/kg. Correlation for these doses on the ascending portion of the curve had greater variance, but was still well correlated (r(2) = 0.92).
CONCLUSIONS
The mouse breathalyzer is an accurate, convenient, noninvasive and well-tolerated method for estimating blood ethanol concentrations in mice across a range of behaviorally relevant concentrations below 2.4 g/kg, especially on the descending limb of the ethanol-time curve. Although this procedure requires a gas chromatograph in the animal facility, the ability to estimate ethanol concentrations quickly and easily will be especially useful in behavioral studies where repeated blood sampling is not feasible.
Topics: Animals; Breath Tests; Ethanol; Mice; Mice, Inbred C57BL
PubMed: 18537938
DOI: 10.1111/j.1530-0277.2008.00737.x -
Journal of Pharmacy & Pharmaceutical... 2019To review knowledge on therapeutic uses of ethanol and the latter's effectiveness and safety profiles in a range of indications. (Review)
Review
PURPOSE
To review knowledge on therapeutic uses of ethanol and the latter's effectiveness and safety profiles in a range of indications.
METHODS
MEDLINE and PubMed databases were searched for relevant peer-reviewed papers published in English between 1888 and 2018 using the following search terms: ethanol, therapeutic, alcohol withdrawal syndrome, antiseptic, antidote, methanol, ethylene glycol, neurolysis, embolization, cyst, sclerosing agent, sclerotherapy, arteriovenous malformations, ablating agent. Studies providing information about association between alcohol and therapeutic indications, or mechanic explanation for the association were included for review.
RESULTS
According to the World Health Organization, approximately three millions deaths worldwide are attributable to alcohol consumption each year. However, the low-to-moderate consumption of ethanol has a number of beneficial effects (mainly on cardiovascular mortality and diabetes). Hence, ethanol has an unusual spectrum of effects that seems interesting for therapeutic purposes. Ethanol's risk-benefit ratio appears to be positive in some therapeutic indications such as antidote to methanol or ethylene glycol poisoning, neurolysis, alcohol withdrawal syndrome, or antiseptic.
CONCLUSION
With the development of interventional radio technologies, and thus extremely precise access to anatomical structures, alcohol has been given new indications - particularly as an embolization, sclerosing or ablation agent. Moreover, constant progress in our knowledge of ethanol's pharmacodynamics might highlight other therapeutic indications for this compound in the future. Ethanol's low cost and wide availability make it a valuable therapeutic agent, compared with other reference treatments. Furthermore, ethanol has a long track record of safety and effectiveness in the indications mentioned above.
Topics: Cardiovascular Diseases; Diabetes Mellitus; Ethanol; Humans
PubMed: 31604058
DOI: 10.18433/jpps30572