EFFECT OF POLYMORPHISM OF THE GABRA2 GENE ON THE DEGREE OF RAT POISONING IN ACUTE ETHANOL INTOXICATION

Four polymorphic GABRA2 gene variations: rs105733011, rs8168342, rs198286814, rs198837638 that can influence the formation of different biological effects of the organism when exposed to ethanol have been investigated. For rs105733011 polymorphism the frequency of occurrence of the CT genotype was found to be significantly higher (p < 0,05) among animals with «severe intoxication» – 37,0% than with «mild intoxication» – 14,0%. For rs198286814 polymorphism the tendency to the most frequent occurrence of the AG genotype in the group of animals with «severe intoxication» was established. Significant differences in the distribution of occurrence frequencies of the GG/AG genotypes in the studied groups for polymorphic loci rs8168342 and rs198837638 were not revealed. It was concluded that the rs105733011 polymorphism can be one of the genetic markers allowing to predict the degree of inhibitory action of ethanol in acute alcohol intoxication.

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The effect of sorbents on the serum levels of copper, iron and their transporting proteins at alcohol intoxication

Kazan medical journal ◽

10.17750/kmj2015-868 ◽

2015 ◽

Vol 96 (5) ◽

pp. 868-871

Author(s):

N A Terekhina ◽

E V Zhidko ◽

G A Terekhin ◽

A G Orbidans

Keyword(s):

Alcohol Abuse ◽

Membrane Permeability ◽

Erythrocyte Membrane ◽

Alcohol Intoxication ◽

Serum Levels ◽

Ethanol Intoxication ◽

Ceruloplasmin Level ◽

Acute Ethanol ◽

Acute Ethanol Intoxication ◽

Erythrocyte Membrane Permeability

Aim. Evaluate the effect of sorbents on erythrocyte membrane permeability and serum levels of copper, iron and their transporting proteins at acute ethanol intoxication. Methods. The study was performed on 94 rats. Acute alcohol intoxication was simulated on intact animals and in animals with prior artificial alcohol abuse. Acute ethanol intoxication was caused by intragastric administration of 40% ethanol at a dose of 0.5 of median lethal dose. Polysorb, Litovit, and Sapropel sorbents were administered at a dose of 3000 mg/kg 30 minutes after ethanol administration. permeability of erythrocyte membrane, serum levels of copper, iron, ceruloplasmin and transferrin were measured by spectrophotometry. Results. Levels of copper and iron in rat serum and erythrocyte membrane permeability significantly dropped compared to the control level at acute ethanol intoxication, ceruloplasmin level raised by 1.5 times, transferrin level did not change significantly. At acute ethanol intoxication in animals with prior artificial alcohol abuse, copper and iron levels and erythrocyte membrane permeability remained low, ceruloplasmin level remained high, transferrin level was decreased for 2 times. All sorbents were able to compensate the serum levels of copper, iron and ceruloplasmin in animals with prior artificial alcohol abuse, and Litovit and Polysorb also influenced on transferrin level. Conclusion. Compensatory effect of Polysorb, Litovit, and Sapropel on the serum levels of ceruloplasmin, copper, iron and transferrin and on erythrocyte membrane permeability was discovered at acute ethanol intoxication in animals with prior artificial alcohol abuse.

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N-acetylcysteine relieves neurologic signs of acute ethanol hangover in rats

Research Results in Pharmacology ◽

10.3897/rrpharmacology.7.62622 ◽

2021 ◽

Vol 7 (1) ◽

pp. 75-83

Author(s):

Denis V. Kurkin ◽

Evgeny I. Morkovin ◽

Nazar A. Osadchenko ◽

Dmitry A. Bakulin ◽

Marina A. Dubrovina ◽

...

Keyword(s):

Motor Skills ◽

Water Maze ◽

Alcohol Intoxication ◽

Cognitive Impairments ◽

Morris Water Maze Test ◽

Fine Motor ◽

Ethanol Intoxication ◽

Maze Test ◽

Acute Ethanol ◽

Acute Ethanol Intoxication

Introduction: Alcohol abuse is one of the grave social and medical problems in many countries, including Russia. Alcohol not only negatively affects health, social and family relationships, but also a person’s performance. Hangover, which is a one of the negative consequences of alcohol intake, is a complex of neurological and somatic symptoms that occur when ethanol is almost completely metabolized to acetaldehyde. This condition, despite the severity and potential economic damage, remains poorly understood, and there are no effective medicines to treat it. Aim: to provide an experimental basis for the possibility of using N-acetylcysteine (NAC), a precursor of glutathione, as a medicine for prevention of the neurological and cognitive impairments due to alcohol intoxication. Materials and Methods: The study used male Wistar rats, which were intraperitoneally injected with ethanol at a dose of 3 g/kg to simulate acute ethanol intoxication. Sixty minutes before the injection, the animals from the experimental groups were gavaged with NAC (1 g/kg) or with an equivalent volume of saline. Immediately after awakening and 3 h after it, the animals were assessed for neurological deficits, motor skills, spontaneous motor activity, and cognitive functions. After the completion of the behavioral tests, the animals were euthanized to assess the level of glutathione, triglycerides (TGs), and malonic dialdehyde (MDA) in liver homogenates, and to determine the activity of enzymatic antioxidant systems and serum aminotransferases. Results and Discussion: The ethanol intoxication in the animals from the control group was associated with pronounced signs of neurological and cognitive impairments, including low spontaneous motor and exploratory activity, impaired fine motor skills in the adhesive test, and cognitive function decline in the Morris water maze test. The rats which had received NAC before ethanol injection demonstrated better fine motor skills in the adhesive test, a higher level of spontaneous motor activity and better performance in the Morris water maze test (in comparison to the animals treated with saline before alcohol intoxication). In the animals which had received NAC, the levels of glutathione, MDA, and TGs, as well as the activity of liver antioxidant enzymes, were closer to the values of the intact rats to a greater extent than in the animals that had been injected with ethanol and received saline. Conclusion: Orally administered NAC before acute ethanol intoxication led to a decrease in the severity of neurological deficiency in rats and reduced the amnesic effect of ethanol. This could be due to an improvement of ethanol metabolism and a decrease in the severity of disorders associated with oxidative stress and liver dysfunction.

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Acute ethanol intoxication induces preferred loss of presynaptic boutons devoid of mitochondria in vivo

10.1101/536334 ◽

2019 ◽

Author(s):

Jil Protzmann ◽

Astha Jaiswal ◽

Karl Rohr ◽

Thomas Kuner ◽

Sidney Cambridge ◽

...

Keyword(s):

Alcohol Intoxication ◽

Blood Alcohol Concentration ◽

Memory Loss ◽

Ethanol Exposure ◽

Dense Core Vesicle ◽

Ethanol Intoxication ◽

Acute Ethanol ◽

Presynaptic Boutons ◽

Acute Ethanol Intoxication

AbstractAcute alcohol intoxication is frequently observed in modern societies and carries a vast burden, ranging from traffic accidents to transient memory loss. Despite years of intense research, the effects of acute ethanol intoxication on brain function remain incompletely understood. Here, we studied the effect of acute ethanol intoxication on axonal organelle trafficking and presynaptic structure using in vivo two photon microscopy in anesthetized mice. After a single intraperitoneal injection of ethanol, inducing a blood alcohol concentration of roughly 250 mg/dl, the axonal mitochondrial mobility was doubled while dense core vesicle mobility remained unaffected. Simultaneously imaging mitochondria and presynaptic boutons revealed that unoccupied presynaptic boutons perished more frequently after ethanol exposure, while boutons stably occupied with mitochondria mostly persisted. Our results define a novel mechanism of ethanol action and may explain difficulties in permanently storing new memories after episodes of intense ethanol consumption with a loss of synapses.

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Toxicological Chemical Analysis of Methanol in Blood of Patients with Acute Ethanol Intoxication for Determining Detectable Quantities of Methanol and Analysis of the Correlation Between Ingested Alcohol

Journal of Biomedical and Clinical Research ◽

10.1515/jbcr-2016-0007 ◽

2016 ◽

Vol 9 (1) ◽

pp. 48-54

Author(s):

Georgi D. Bonchev ◽

Snezha Z. Zlateva ◽

Marieta I. Yovcheva

Keyword(s):

Chemical Analysis ◽

Limit Of Detection ◽

Alcohol Intoxication ◽

Poor Quality ◽

Acute Alcohol Intoxication ◽

Limit Of Quantification ◽

Flame Ionization ◽

Acute Ethanol ◽

Acute Ethanol Intoxication ◽

Major Factors

Summary The aim of the study was to carry out a toxicological chemical analysis of methanol in detectable quantities in the blood of patients with acute alcohol intoxication. Blood samples from 85 patients with acute alcohol intoxication were analysed for the presence of methanol. All patients with acute methanol intoxication were excluded from the study. The methods of gas chromatography with vapor-phase analysis (head-space) and flame ionization detection (FID) were used. The limit of detection (LOD=0.015 g/L) and the limit of quantification (LOQ=0.025 g/L) of methanol in whole blood were evaluated. In 30% of the cases, methanol was found in the blood in detectable quantities. The levels of methanol were on the average 5 to 6 times lower than the toxic methanol level (0200 g/L) and they were not due to natural metabolic processes (ingestion of fruit, fruit juices or vegetables). No reliable statistically linear correlation between the concentration of ethanol and methanol was found. Methanol subintoxications are major factors in alcohol intoxications, in which the quantity of the alcohol ingested is not as important as its quality. Chronic methanol subintoxication of people who often consume alcohol of poor quality is discussed.

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Acute and chronic ethanol consumption differentially impact pathways limiting hepatic protein synthesis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00026.2008 ◽

2008 ◽

Vol 295 (1) ◽

pp. E3-E9 ◽

Cited By ~ 21

Author(s):

Anne M. Karinch ◽

Jonathan H. Martin ◽

Thomas C. Vary

Keyword(s):

Protein Synthesis ◽

Alcohol Intoxication ◽

Ethanol Consumption ◽

Chronic Alcohol ◽

Ethanol Intoxication ◽

Initiation Factors ◽

Eif2α Phosphorylation ◽

Acute Ethanol ◽

Acute Ethanol Intoxication ◽

Hepatic Protein Synthesis

This review identifies the various pathways responsible for modulating hepatic protein synthesis following acute and chronic alcohol intoxication and describes the mechanism(s) responsible for these changes. Alcohol intoxication induces a defect in global protein synthetic rates that is localized to impaired translation of mRNA at the level of peptide-chain initiation. Translation initiation is regulated at two steps: formation of the 43S preinitiation complex [controlled by eukaryotic initiation factors 2 (eIF2) and 2B (eIF2B)] and the binding of mRNA to the 40S ribosome (controlled by the eIF4F complex). To date, alcohol-induced alterations in eIF2 and eIF2B content and activity are best investigated. Ethanol decreases eIF2B activity when ingested either acutely or chronically. The reduced eIF2B activity most likely is a consequence of twofold increased phosphorylation of the α-subunit of eIF2 on Ser51 following acute intoxication. The increase in eIF2α phosphorylation after chronic alcohol consumption is the same as that induced by acute ethanol intoxication, and protein synthesis is not further reduced by long-term alcohol ingestion despite additional reduced expression of initiation factors and elongation factors. eIF2α phosphorylation alone appears sufficient to maximally inhibit hepatic protein synthesis. Indeed, pretreatment with Salubrinal, an inhibitor of eIF2α(P) phosphatase, before ethanol treatment does not further inhibit protein synthesis or increase eIF2α phosphorylation, suggesting that acute ethanol intoxication causes maximal eIF2α phosphorylation elevation and hepatic protein synthesis inhibition. Ethanol-induced inhibition of hepatic protein synthesis is not rapidly reversed by cessation of ethanol consumption. In conclusion, sustained eIF2α phosphorylation is a hallmark of excessive alcohol intake leading to inhibition of protein synthesis. Enhanced phosphorylation of eIF2α represents a unique response of liver to alcohol intoxication, because the ethanol-induced elevation of eIF2α(P) is not observed in skeletal muscle or heart.

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Heavy Ethanol Intoxication Increases Proinflammatory Cytokines and Aggravates Hemorrhagic Shock-Induced Organ Damage in Rats

Mediators of Inflammation ◽

10.1155/2013/121786 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Tsung-Ming Hu ◽

Ru-Ping Lee ◽

Chung-Jen Lee ◽

Yi-Maun Subeq ◽

Nien-Tsung Lin ◽

...

Keyword(s):

Hemorrhagic Shock ◽

Alcohol Intoxication ◽

Lactic Dehydrogenase ◽

Serum Levels ◽

Organ Damage ◽

Ethanol Intoxication ◽

Total Blood ◽

Cytokine Levels ◽

Acute Ethanol ◽

Acute Ethanol Intoxication

Hemorrhagic shock (HS) following acute alcohol intoxication can increase proinflammatory cytokine production and induce marked immunosuppression. We investigated the effects of ethanol on physiopathology and cytokine levels following HS in acutely alcohol-intoxicated rats. Rats received an intravenous injection of 5 g/kg ethanol over 3 h followed by HS induced by withdrawal of 40% of total blood volume from a femoral arterial catheter over 30 min. Mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 48 h after the start of blood withdrawal. Biochemical parameters, including hemoglobin, ethanol, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), and creatine phosphokinase (CPK), were measured at 30 min before induction of HS and 0, 1, 3, 6, 9, 12, 18, 24, and 48 h after HS. Serum tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) levels were measured at 1 and 12 h after HS. The liver, kidneys, and lungs were removed for pathology at 48 h later. HS significantly increased HR, blood GOT, GPT, BUN, Cre, LDH, CPK, TNF-α, and IL-6 levels and decreased hemoglobin and MAP in rats. Acute ethanol intoxication further increased serum levels of GOT, GPT, BUN, Cre, LDH, CPK, TNF-αand IL-6 elevation following HS. Acutely intoxicated rats exacerbated the histopathologic changes in the liver, kidneys, and lungs following HS.

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