Schisantherin A alleviated alcohol-induced liver injury by the regulation of alcohol metabolism and NF-kB pathway

Alcohol consumption is a common custom worldwide, and the toxic effects of alcohol on several target organs are well understood. The liver is the primary site of alcohol metabolism and is therefore the major target of alcohol toxicity. Alcoholic liver disease is a spectrum of disease states, ranging from simple steatosis (fat accumulation), to inflammation, and eventually to fibrosis and cirrhosis if untreated. The fibrotic stage of ALD is primarily characterized by robust accumulation of extracellular matrix (ECM) proteins (collagens) which ultimately impairs the function of the organ. The role of the ECM in early stages of ALD is poorly understood, but recent research has demonstrated that a number of changes in the hepatic ECM in prefibrotic ALD not only are present, but may also contribute to disease progression. The purpose of this review is to summarize the established and proposed changes to the hepatic extracellular matrix (ECM) that may contribute to earlier stages of ALD development and to discuss potential mechanisms by which these changes may mediate the progression of the disease.

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Chronic intake of high-dose of blueberry leaf extract does not augment the harmful effects of ethanol in rats

PeerJ ◽

10.7717/peerj.6989 ◽

2019 ◽

Vol 7 ◽

pp. e6989 ◽

Cited By ~ 2

Author(s):

Kaede Yamasaki ◽

Kazuhiro Sugamoto ◽

Teruaki Arakawa ◽

Kazuo Nishiyama ◽

Masao Yamasaki

Keyword(s):

Body Weight ◽

Liver Injury ◽

Leaf Extract ◽

Diet Group ◽

Liquid Diet ◽

High Dose ◽

Alcohol Metabolism ◽

Carbonyl Protein ◽

Harmful Effects ◽

Expression And Activity

Excessive alcohol consumption is a risk factor for liver diseases. Enhancement of alcohol metabolism could be an effective strategy to prevent these adverse effects since it promotes the clearance of ethanol and acetaldehyde from the serum. Polyphenol-rich products have shown to protect against alcohol-related liver damage. Blueberry leaves have attracted attention as they are rich polyphenols such as proantocyanidins and chlorogenic acid. In this study, we investigated the effects of a high dose of blueberry leaf extract (BLEx) on alcohol metabolism during chronic intake of ethanol. Seven-week old Sprague-Dawley (SD) rats were divided into four groups: normal liquid diet group (NLD), normal liquid diet + BLEx group (NLD + BLEx), alcohol liquid diet group (ALD), and alcohol liquid diet + BLEx (ALD + BLEx). Then, rats were fed experimental diet for 5 weeks and at the end of feeding period, body weight, food intake, liver weight, indices of liver injury, expression and activity of alcohol metabolism-related and anti-oxidative enzymes, and levels of carbonyl protein, triglyceride (TG), and total cholesterol (T-Chol) were measured. Body weight and food intake decreased, whereas liver aldehyde dehydrogenase (ALDH) activity, liver microsomal cytochrome P450 2E1 (CYP2E1) protein and mRNA expression, and heme oxygenase 1 (HO-1) mRNA expression were upregulated by ethanol intake. Dietary BLEx, however, did not affect any of these ethanol-related changes. Indices of liver injury, expression and activity of other alcohol metabolism-related enzymes, liver carbonyl protein, TG, and T-Chol levels were not altered by ethanol and BLEx. Thus, chronic BLEx intake does not ameliorate the harmful effects of ethanol.

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Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcoholic liver disease

10.1101/2020.08.25.267096 ◽

2020 ◽

Author(s):

Yilin Yang ◽

Panjamaporn Sungwung ◽

Yirang Jung ◽

Reiichiro Kondo ◽

Matthew McConnell ◽

...

Keyword(s):

Liver Injury ◽

Gene Delivery ◽

Heat Shock Protein 90 ◽

No Production ◽

Alcohol Metabolism ◽

Histone Deacetylase 6 ◽

Liver Sinusoidal Endothelial Cells ◽

Adeno Associated Virus ◽

Key Enzyme ◽

Endothelial Nitric Oxide

AbstractBackgroundIt is unknown whether liver sinusoidal endothelial cells (LSECs) metabolize alcohol. Chronic alcohol consumption decreases endothelial nitric oxide synthase (eNOS)-derived NO production typical of LSEC dysfunction. Heat shock protein 90 (Hsp90) interacts with eNOS to increase its activity. Cytochrome P450 2E1 (CYP2E1) is a key enzyme in alcohol metabolism and facilitates protein acetylation via acetyl-CoA, but its expression in LSECs is unknown. This study investigates alcohol metabolism by LSECs, the mechanism of alcohol-induced LSEC dysfunction and a potential therapeutic approach for alcohol-induced liver injury.MethodsPrimary human, rat and mouse LSECs were used. Histone deacetylase 6 (HDAC6) was overexpressed specifically in liver ECs using an adeno-associated virus (AAV)-mediated gene delivery system to decrease Hsp90 acetylation in ethanol fed mice.ResultsLSECs expressed CYP2E1 and alcohol dehydrogenase 1 (ADH1) and metabolized alcohol. Ethanol induced CYP2E1 in LSECs, but not ADH1. Alcohol metabolism by CYP2E1 increased Hsp90 acetylation and decreased its interaction with eNOS along with a decrease in NO production. A non-acetylation mutant of Hsp90 increased its interaction with eNOS and NO production, whereas a hyper-acetylation mutant decreased NO production, compared with wildtype Hsp90. These results indicate that Hsp90 acetylation is responsible for decreases in its interaction with eNOS and eNOS-derived NO production. Adeno-associated virus 8 (AAV8)-driven HDAC6 overexpression specifically in liver ECs deacetylated Hsp90, restored Hsp90’s interaction with eNOS and ameliorated alcohol-induced liver injury in mice.ConclusionRestoring LSEC function is important for ameliorating alcohol-induced liver injury. To this end, blocking acetylation of Hsp90 specifically in LSECs via AAV-mediated gene delivery has the potential to be a new therapeutic strategy.

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MOLECULAR ASPECTS OF ALCOHOL METABOLISM: Transcription Factors Involved in Early Ethanol-Induced Liver Injury

Annual Review of Nutrition ◽

10.1146/annurev.nutr.24.012003.132258 ◽

2004 ◽

Vol 24 (1) ◽

pp. 55-78 ◽

Cited By ~ 100

Author(s):

Laura E. Nagy

Keyword(s):

Transcription Factors ◽

Liver Injury ◽

Alcohol Metabolism ◽

Molecular Aspects

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Effects of Steroids on Fetal Rat Liver

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100063664 ◽

1969 ◽

Vol 27 ◽

pp. 350-351

Author(s):

F. G. Zaki

Keyword(s):

Liver Injury ◽

Rat Liver ◽

Fetal Liver ◽

Dosage Level ◽

Maternal Plasma ◽

Methyl Prednisolone ◽

Fetal Rat ◽

Toxic Agents ◽

Fetal Rat Liver ◽

Neonatal Liver

Fetal and neonatal liver injury induced by agents circulating in maternal plasma, even though well recognized, its morphological manifestations are not yet established. As part of our studies of fetal and neonatal liver injury induced by maternal nutritional disorders, metabolic impairment and toxic agents, the effects of two anti-inflammatory steroids have been recently inves tigated.Triamcinolone and methyl prednisolone were injected each in a group of rats during pregnancy at a-dosage level of 2 mgm three times a week. Fetal liver was studied at 18 days of gestation. Litter size and weight markedly decreased than those of control rats. Stillbirths and resorption were of higher incidence in the triamcinolone group than in those given the prednisolone.

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