scholarly journals Protective effect of corn peptides against alcoholic liver injury in men with chronic alcohol consumption: a randomized double-blind placebo-controlled study

2014 ◽  
Vol 13 (1) ◽  
pp. 192 ◽  
Author(s):  
Yuhong Wu ◽  
Xingchang Pan ◽  
Shixiu Zhang ◽  
Wenxian Wang ◽  
Muyi Cai ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Liver Injury ◽  
Protective Effect ◽  
Controlled Study ◽  
Alcoholic Liver Injury ◽  
Chronic Alcohol ◽  
Double Blind ◽  
Chronic Alcohol Consumption ◽  
Double Blind Placebo

scholarly journals The Role of Alcohol Consumption on Acetaminophen Induced Liver Injury: Implications from A Mathematical Model

2020 ◽  
Author(s):  
Aditi Ghosh ◽  
Isaac Berger ◽  
Christopher H. Remien ◽  
Anuj Mubayi
Keyword(s):  
Mathematical Model ◽  
Alcohol Consumption ◽  
Liver Injury ◽  
Protective Effect ◽  
The Body ◽  
Chronic Alcohol ◽  
Single Time ◽  
Apap Overdose ◽  
Increased Risk

AbstractAcetaminophen (APAP) overdose is one of the predominant causes of drug induced acute liver injury in the U.S and U.K. Clinical studies show that ingestion of alcohol may increase the risk of APAP induced liver injury. Chronic alcoholism may potentiate APAP hepatotoxicity and this increased risk of APAP toxicity is observed when APAP is ingested even shortly after alcohol is cleared from the body. However, clinical reports also suggest that acute alcohol consumption may have a protective effect against hepatotoxicity by inhibiting microsomal acetaminophen oxidation and thereby reducing N-acetyl-p-benzoquinone imine (NAPQI) production. The aim of this study is to model this dual role of alcohol to determine how the timing of alcohol ingestion affects APAP metabolism and resulting liver injury and identify mechanisms of APAP induced liver injury. The mathematical model is developed to capture condition of a patient of single time APAP overdose who may be an acute or chronic alcohol user. The analysis suggests that the risk of APAP-induced hepatotoxicity is increased if APAP is ingested shortly after alcohol is cleared from the body in chronic alcohol users. A protective effect of acute consumption of alcohol is also observed in patients with APAP overdose. For example, simultaneous ingestion of alcohol and APAP overdose or alcohol intake after or before few hours of APAP overdose may result in less APAP-induced hepatotoxicity when compared to a single time APAP overdose. The rate of hepatocyte damage in APAP overdose patients depends on trade-off between induction and inhibition of CYP enzyme.

Chronic Alcohol Consumption Increased Bile Acid Levels in Enterohepatic Circulation and Reduced Efficacy of Irinotecan

2020 ◽  
Vol 55 (3) ◽  
pp. 264-277
Author(s):  
Xia Gong ◽  
Qisong Zhang ◽  
Yanjiao Ruan ◽  
Ming Hu ◽  
Zhongqiu Liu ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Liver Injury ◽  
Enterohepatic Circulation ◽  
Ethanol Intake ◽  
Mass Spectrometry Analysis ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Chronic Alcohol ◽  
Chronic Alcohol Consumption ◽  
Chronic Ethanol Consumption

Abstract Aims To investigate the effect of ethanol intake on the whole enterohepatic circulation (EHC) of bile acids (BAs) and, more importantly, on pharmacokinetics of irinotecan. Methods The present study utilized a mouse model administered by gavage with 0 (control), 240 mg/100 g (30%, v/v) and 390 mg/100 g (50%, v/v) ethanol for 6 weeks, followed by BA profiles in the whole EHC (including liver, gallbladder, intestine and plasma) and colon using ultra-high performance liquid chromatography with tandem mass spectrometry analysis. Pharmacokinetic parameters of irinotecan were measured after administration of irinotecan (i.v. 5 mg/kg) on alcohol-treated mice. Results The results showed that compared with the control group, concentrations of most free-BAs, total amount of the three main forms of BAs (free-BA, taurine-BA and glycine-BA) and total BAs (TBAs) in 50% ethanol intake group were significantly increased, which are mostly attributed to the augmentation of free-BAs and taurine-BAs. Additionally, the TBAs in liver and gallbladder and the BA pool were markedly increased in the 30% ethanol intake group. Importantly, ethanol intake upregulated the expression of BA-related enzymes (Cyp7a1, Cyp27a1, Cyp8b1 and Baat) and transporters (Bsep, Mrp2, P-gp and Asbt) and downregulated the expression of transporter Ntcp and nuclear receptor Fxr in the liver and ileum, respectively. Additionally, 50% ethanol intake caused fairly distinct liver injury. Furthermore, the AUC0–24 h of irinotecan and SN38 were significantly reduced but their clearance was significantly increased in the disrupted EHC of BA by 50% ethanol intake. Conclusions The present study demonstrated that ethanol intake altered the expression of BA-related synthetases and transporters. The BA levels, especially the toxic BAs (chenodeoxycholic acid, deoxycholic acid and lithocholic acid), in the whole EHC were significantly increased by ethanol intake, which may provide a potential explanation to illuminate the pathogenesis of alcoholic liver injury. Most importantly, chronic ethanol consumption had a significant impact on the pharmacokinetics (AUC0–24 h and clearance) of irinotecan and SN38; hence colon cancer patients with chronic alcohol consumption treated with irinotecan deserve our close attention.

Chronic alcohol consumption accelerates liver injury in T cell-mediated hepatitis: alcohol disregulation of NF-κB and STAT3 signaling pathways

2004 ◽  
Vol 287 (2) ◽  
pp. G471-G479 ◽  
Author(s):  
Barbara Jaruga ◽  
Feng Hong ◽  
Won-Ho Kim ◽  
Rui Sun ◽  
Saijun Fan ◽  
...  
Keyword(s):  
T Cell ◽  
Alcohol Consumption ◽  
Liver Injury ◽  
Hepatitis Virus ◽  
Chronic Alcohol ◽  
Con A ◽  
Control Pair ◽  
Chronic Alcohol Consumption ◽  
Chronic Ethanol Consumption ◽  
Adhesive Molecules

Alcohol consumption is a major risk factor accelerating the progression of liver disease in patients with chronic hepatitis virus infection. However, the mechanism underlying the enhanced susceptibility of alcoholics to liver injury is not fully understood. Here, we demonstrate that chronic ethanol consumption increases the susceptibility of C57BL/6 mice to concanavalin A (Con A)-induced T cell-mediated hepatitis. Injection of a low dose of Con A (5 μg/g) causes severe liver damage in ethanol-fed mice as evidenced by a significant elevation of serum alanine aminotransaminase levels, massive necrosis, and infiltration of leukocytes but only slightly induces liver injury in control pair-fed mice. In ethanol-fed mice, the activation and cytotoxicity of natural killer T cells, cells that play key roles in Con A-induced T cell hepatitis, are not significantly enhanced relative to pair-fed mice. Moreover, Con A-induced activation of hepatic NF-κB is increased, whereas activation of STAT1 and STAT3 is attenuated in ethanol-fed mice. Consistent with this result, the expression of chemokines and adhesion molecules [such as ICAM-1, macrophage inflammatory protein (MIP)-1, MIP-2, and MCP-1] controlled by NF-κB is upregulated, whereas STAT1-controlled expression of chemokines (such as MIG and IP-10) is downregulated in ethanol-fed mice compared with pair-fed mice. In conclusion, chronic alcohol consumption accelerates T cell-mediated hepatitis via upregulation of the NF-κB signaling pathway and subsequently enhances expression of chemokines/adhesive molecules and recruitment of leukocytes into the liver. Downregulation of the antiapoptotic STAT3 signal may also contribute to alcohol potentiation of T cell hepatitis.

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