Molecular mechanisms of ethanol biotransformation: enzymes of oxidative and nonoxidative metabolic pathways in human

Kubiak-Tomaszewska, Grażyna; Tomaszewski, Piotr; Pachecka, J; Struga, Marta; Olejarz, Wioletta; Mielczarek-Puta, Magdalena; Nowicka, Grażyna

doi:10.1080/00498254.2020.1761571

Cited by 14 publications

(21 citation statements)

References 139 publications

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“…SIRT1 is highly sensitive to intracellular oxidation state. In addition to the main oxidative metabolism pathways mentioned above, both the reaction catalyzed by microsomal CYPs, mainly CYP2E1,and the pathway mediated by peroxisomal CAT, compose a small percentage of alcohol oxidation [20,21].The unfavorable products of oxidative metabolism in ALD, including acetaldehyde and acetate, may ultimately down-regulate hepatic SIRT1 and activity [22]. Interestingly, deletion of SIRT1 drastically exacerbates ethanol mediated oxidative stress, indicating that the inhibition of SIRT1 in ALD may format a feedback loop to further suppress SIRT1 through ROS production [15].…”

Section: Ivyspring International Publishermentioning

confidence: 99%

Emerging Roles of SIRT1 in Alcoholic Liver Disease

Ren¹,

Wang²,

Wu³

et al. 2020

Int. J. Biol. Sci.

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Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease worldwide with a wide spectrum of liver pathologies ranging from simple steatosis to steatohepatitis, cirrhosis, and even hepatocellular carcinoma. It has been demonstrated that ALD is mediated in whole or in part by a central signaling molecule sirtuin 1 (SIRT1), a conserved class III histone deacetylase.SIRT1 plays beneficial roles in regulating hepatic lipid metabolism, inhibiting hepatic inflammation, controlling hepatic fibrosis and mediating hepatocellular carcinoma in ALD. However, underlying molecular mechanisms are complex and remain incompletely understood. The aim of this review was to highlight the latest advances in understanding of SIRT1 regulatory mechanisms in ALD and discuss their unique potential role as novel therapeutic target for ALD treatment.

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Section: Ivyspring International Publishermentioning

confidence: 99%

Emerging Roles of SIRT1 in Alcoholic Liver Disease

Ren¹,

Wang²,

Wu³

et al. 2020

Int. J. Biol. Sci.

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“…The model of rats used to evaluate the hypolipidemic effects of HeECo was obtained by acute ethanol administration. After the ingestion of ethanol, about 90% is metabolized in the liver through oxidative reactions [18][19] in the cytosol. The ethanol is transformed to acetaldehyde catalyzed by alcohol dehydrogenase (ADH).…”

Section: Discussionmentioning

confidence: 99%

Untitled

2023

IJPSR

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Hydroethanolic extract of the Cedrela odorata (HeECo) showed hypolipidemic potential in diabetic rats. Thus, we evaluate the hypolipidemic effect and the mechanism of the action of the HeECo in a rat model of ethanolinduced hyperlipidemia. Male Wistar rats are divided: normolipidemic (C); hyperlipidemic non-treated (Hl); hyperlipidemic treated with HeECo 500 mg.kg -1 (HlCo); and hyperlipidemic treated with fenofibrate 200 mg.kg -1 (HlFen). The relative weight, lipid content of some tissues, serum lipid profile, enzymatic activity and content of lipase lipoprotein (LPL) in retroperitoneal white adipose tissue (retWAT) were measured. Protein content of SREBP-1c and enzyme activities of glucose-6-phosphate dehydrogenase (G6PD), malic enzyme and ATP-citrate lyase (ACL) were measured in the liver. We observed an increase in the levels of triacylglycerol, total cholesterol and VLDL in the Hl group that the C group. The HlCo group showed reduced serum parameters, relative weight, lipid content and LPL activity in retWAT, that the Hl group. We observed lower activity in G6PD and ACL in the HlCo group that the Hl group. We suggest that HeECo has a hypolipidemic effect, possibly reducing de novo fatty acid synthesis in the liver. INTRODUCTION:Dyslipidemia is a known disorder in lipid metabolism with an increase in cholesterol and triglycerides (TAG) in the plasma 1-2 . It is among the main risk factors for atherosclerosis, myocardial infarction and stroke. The reduction of blood lipids is an important strategy for preventing the occurrence and progression of these diseases.

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“…Using 3'-phosphoadenosine 5'-phosphosulfate as a sulfonyl donor, less than 0.1% of ethanol is transformed by sulfotransferases (SULTs) into ethyl sulfate (EtS), which is readily excreted in urine [ 12 ]. SULT1A1, SULT1A3, SULT1B1, SULT1C2, and SULT2A1 in the liver show appreciable affinities for ethanol [ 13 ]. In one study, the expression levels of SULT1A1 and SULT2A1 in the liver and intestine of rats were increased after 2 weeks of ethanol intake [ 14 ].…”

Section: Ethanol Metabolismmentioning

confidence: 99%

Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease

Yan

et al. 2023

J Transl Med

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Alcoholism is a widespread and damaging behaviour of people throughout the world. Long-term alcohol consumption has resulted in alcoholic liver disease (ALD) being the leading cause of chronic liver disease. Many metabolic enzymes, including alcohol dehydrogenases such as ADH, CYP2E1, and CATacetaldehyde dehydrogenases ALDHsand nonoxidative metabolizing enzymes such as SULT, UGT, and FAEES, are involved in the metabolism of ethanol, the main component in alcoholic beverages. Ethanol consumption changes the functional or expression profiles of various regulatory factors, such as kinases, transcription factors, and microRNAs. Therefore, the underlying mechanisms of ALD are complex, involving inflammation, mitochondrial damage, endoplasmic reticulum stress, nitrification, and oxidative stress. Moreover, recent evidence has demonstrated that the gut-liver axis plays a critical role in ALD pathogenesis. For example, ethanol damages the intestinal barrier, resulting in the release of endotoxins and alterations in intestinal flora content and bile acid metabolism. However, ALD therapies show low effectiveness. Therefore, this review summarizes ethanol metabolism pathways and highly influential pathogenic mechanisms and regulatory factors involved in ALD pathology with the aim of new therapeutic insights.

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Molecular mechanisms of ethanol biotransformation: enzymes of oxidative and nonoxidative metabolic pathways in human

Cited by 14 publications

References 139 publications

Emerging Roles of SIRT1 in Alcoholic Liver Disease

Emerging Roles of SIRT1 in Alcoholic Liver Disease

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Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease

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