Ethanol Metabolism, Oxygen Availability and Alcohol Induced Liver Damage

Israel, Yedy; Kalant, H.; Jm, Khanna; Orrego, H; Mj, Phillips; Dj, Stewart

doi:10.1007/978-1-4899-5181-6_22

Cited by 8 publications

(5 citation statements)

References 28 publications

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“…Acetaldehyde is the major toxin in ethanol-induced liver injury, causing cellular damage, inflammation and fibrosis (9). Acetaldehyde also increases the redox ratio of nicotinamide adenine dinucleotide (NADH/NAD + ) leading to a reduction of fatty acid ßoxidation through a reduction of PPARα activity (4,10). Activation of hepatic lipogenesis is another important biochemical characteristic of hepatic steatosis in AFLD development (11).…”

Section: Introductionmentioning

confidence: 99%

SCD1 deficiency protects mice against ethanol-induced liver injury

Lounis

Escoula

Veillette

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Stearoyl-CoA desaturase 1 (SCD1) is a delta-9 fatty acid desaturase that catalyzes the synthesis of mono-unsaturated fatty acids (MUFA). SCD1 is a critical control point regulating hepatic lipid synthesis and β-oxidation. Scd1 KO mice are resistant to the development of diet-induced non-alcoholic fatty liver disease (NAFLD). Using a chronic-binge protocol of ethanol-mediated liver injury, we aimed to determine if these KO mice are also resistant to the development of alcoholic fatty liver disease (AFLD). Mice fed a low-fat diet (especially low in MUFA) containing 5% ethanol for 10days, followed by a single ethanol (5g/kg) gavage, developed severe liver injury manifesting as hepatic steatosis. This was associated with an increase in de novo lipogenesis and inflammation. Using this model, we show that Scd1 KO mice are resistant to the development of AFLD. Scd1 KO mice do not show accumulation of hepatic triglycerides, activation of de novo lipogenesis nor elevation of cytokines or other pro-inflammatory markers. Incubating HepG2 cells with a SCD1 inhibitor induced a similar resistance to the effect of ethanol, confirming a role for SCD1 activity in mediating ethanol-induced hepatic injury. Taken together, our study shows that SCD1 is a key player in the development of AFLD and associated deleterious effects, and suggests SCD1 inhibition as a therapeutic option for the treatment of this hepatic disease.

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Section: Introductionmentioning

confidence: 99%

SCD1 deficiency protects mice against ethanol-induced liver injury

Lounis

Escoula

Veillette

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…In a previous study, increased oxidation of ethanol was accompanied by increased total hepatic oxygen utilization, as studied in whole animals, after chronic ethanol administration. Also, oxygen exposure produced major elevations in serum glutamate oxaloacetic transferase (SGOT) and serum ornithine carbamyl transferase (SOCT) activities, suggesting that oxygen may protect against alcoholic liver damage (Israel et al., 1977).…”

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confidence: 99%

Influence of Dissolved Oxygen Concentration on the Pharmacokinetics of Alcohol in Humans

Baek

Lee

Kwon

2010

Alcoholism Clin & Exp Res

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“…These data imply a shorter time required for sobering up. In support of this, previous studies have found that the elimination rate of ethanol was increased by 60% in monkeys which received oxygenated drinking water (Hyva¨rinen et al, 1978); increased oxidation of ethanol in animals was accompanied by a higher level of total hepatic oxygen utilization after chronic ethanol administration (Israel et al, 1977); and ethanol oxidation in isolated perfused rat liver was elevated in the presence of an increased partial pressure of oxygen in the aerating medium (Gordon, 1968;Videla and Israel, 1970).In contrast, other studies have reported no significant differences in the pharmacokinetics of alcohol between normal groups and those receiving increased levels of oxygen by inhalation or in drinking water (Fleming and Reynolds, 1935;Laakso et al, 1979;Maring and von Wartburg, 1980). However, as these data were reported more than 20 years ago, it is reasonable to assume that our clinical study represents a higher level of scientific efficacy.…”

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confidence: 56%

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confidence: 58%

Oxygenated Alcohol – Sober Faster!

Baek

Lee

Jeong

et al. 2010

Alcoholism Clin & Exp Res

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blood alcohol concentrations to 0.000 and 0.050% faster than normal levels of dissolved oxygen in alcohol.The oxygen-enriched spirit Soju, launched in 2007, contains 19.5% (v ⁄ v) ethanol and is the most popular alcoholic drink in Korea. The concentration of dissolved oxygen in this alcoholic beverage can be increased to 25 ppm by the patented method of Sunyang Co., Ltd., Korea. Recently, there has been extensive publicity surrounding the suggestion that a high concentration of dissolved oxygen in alcohol may help reduce alcohol-related side effects; however, scientific evidence for this claim is lacking. Therefore, we investigated the effect of dissolved oxygen on the pharmacokinetics of alcohol in healthy volunteers (Baek et al., 2010). We found that elevated dissolved oxygen concentrations in alcoholic drinks shortened the time required for the blood alcohol concentration (BAC) to reach 0.000% or 0.050%, without causing a significant difference in the maximum BAC (C max ) or the time to reach the maximum BAC (T max ) after alcohol ingestion.The publication of our results in Alcoholism: Clinical and Experimental Research has created worldwide interest, and Lachenmeier and Rehm (2010) have provided some valuable comments on the article. In this reply, we respond to these remarks and describe some supplementary results, which further explain the effects of different concentrations of dissolved oxygen on alcohol pharmacokinetics.The conclusion of our research was that high concentrations of dissolved oxygen (20 or 25 ppm) in alcoholic beverages decrease the time required to reach a BAC of 0.000 or 0.050%, compared with the time required after consumption of alcoholic beverages containing a normal concentration of dissolved oxygen (8 ppm). These data imply a shorter time required for sobering up. In support of this, previous studies have found that the elimination rate of ethanol was increased by 60% in monkeys which received oxygenated drinking water (Hyva¨rinen et al., 1978); increased oxidation of ethanol in animals was accompanied by a higher level of total hepatic oxygen utilization after chronic ethanol administration (Israel et al., 1977); and ethanol oxidation in isolated perfused rat liver was elevated in the presence of an increased partial pressure of oxygen in the aerating medium (Gordon, 1968;Videla and Israel, 1970).In contrast, other studies have reported no significant differences in the pharmacokinetics of alcohol between normal groups and those receiving increased levels of oxygen by inhalation or in drinking water (Fleming and Reynolds, 1935;Laakso et al., 1979;Maring and von Wartburg, 1980). However, as these data were reported more than 20 years ago, it is reasonable to assume that our clinical study represents a higher level of scientific efficacy. Our methodologies and analyses were more advanced, and the use of a randomized, 2-period cross-over design minimized variability. Furthermore, while the numbers of human or animal subjects in the earlier studies were minimal, the sample size in ou...

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Ethanol Metabolism, Oxygen Availability and Alcohol Induced Liver Damage

Cited by 8 publications

References 28 publications

SCD1 deficiency protects mice against ethanol-induced liver injury

SCD1 deficiency protects mice against ethanol-induced liver injury

Influence of Dissolved Oxygen Concentration on the Pharmacokinetics of Alcohol in Humans

Oxygenated Alcohol – Sober Faster!

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