Chronic ethanol and high glucose inducible CYP2E1 mediated oxidative stress leads to greater cellular injury in VL-17A cells: a potential mechanism for liver injury due to chronic alcohol consumption and hyperglycemia

2013 ◽  
Vol 2 (4) ◽  
pp. 245 ◽  
Author(s):  
Kavitha Swaminathan ◽  
S. Mathan Kumar ◽  
Dahn L. Clemens ◽  
Aparajita Dey
Keyword(s):  
Oxidative Stress ◽  
Alcohol Consumption ◽  
Liver Injury ◽  
High Glucose ◽  
Chronic Ethanol ◽  
Cellular Injury ◽  
Chronic Alcohol ◽  
Potential Mechanism ◽  
Chronic Alcohol Consumption

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.

scholarly journals Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease

2019 ◽  
Vol 60 (5) ◽  
pp. 922-936 ◽  
Author(s):  
Hongwu Wang ◽  
Ting Wu ◽  
Yaqi Wang ◽  
Xiaoyang Wan ◽  
Junying Qi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Liver Disease ◽  
Alcohol Consumption ◽  
Regulatory T Cells ◽  
Alcoholic Liver Disease ◽  
Lipid Accumulation ◽  
Chronic Alcohol ◽  
Chronic Alcohol Consumption ◽  
Alcoholic Fatty Liver

Sensitization of hepatic immune cells from chronic alcohol consumption gives rise to inflammatory accumulation, which is considered a leading cause of liver damage. Regulatory T cells (Tregs) are an immunosuppressive cell subset that plays an important role in a variety of liver diseases; however, data about pathological involvement of Tregs in liver steatosis of alcoholic liver disease (ALD) is insufficient. In mouse models of ALD, we found that increased lipid accumulation by chronic alcohol intake was accompanied by oxidative stress, inflammatory accumulation, and Treg decline in the liver. Adoptive transfer of Tregs relieved lipid metabolic disorder, oxidative stress, inflammation, and, consequently, ameliorated the alcoholic fatty liver. Macrophages are a dominant source of inflammation in ALD. Aberrant macrophage activation and cytokine production were activated during chronic alcohol consumption, but were significantly inhibited after Treg transfer. In vitro, macrophages were co-activated by alcohol and lipopolysaccharide to mimic a condition for alcoholic liver microenvironment. Tregs suppressed monocyte chemoattractant protein-1 and TNF-α production from these macrophages. However, such effects of Tregs were remarkably neutralized when interleukin (IL)-10 was blocked. Altogether, our data uncover a novel role of Tregs in restoring liver lipid metabolism in ALD, which partially relies on IL-10-mediated suppression of hepatic pro-inflammatory macrophages.

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.

scholarly journals Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Ravi Varatharajalu ◽  
Mamatha Garige ◽  
Leslie C. Leckey ◽  
Karina Reyes-Gordillo ◽  
Ruchi Shah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Therapeutic Potential ◽  
Protective Role ◽  
Chronic Ethanol ◽  
Paraoxonase 1 ◽  
Protective Effects ◽  
Chronic Alcohol ◽  
Ethanol Group ◽  
Homocysteine Thiolactonase

Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories fromω-3 polyunsaturated fatty acids (PUFA)) and Lieber-deCarli high menhaden (13.8% of total calories fromω-3 PUFA) alcohol-liquid (5%) diets supplemented with or without curcumin (150 mg/kg/day) for 8 weeks. Treatment with curcumin protected against highω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1) mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to highω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with highω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and highω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis.

Chronic Alcohol Consumption and Cerebral Indices of Oxidative Stress: Is There a Link?

2001 ◽  
Vol 25 (5) ◽  
pp. 717-725 ◽  
Author(s):  
M. E. Gotz ◽  
B. Janetzky ◽  
S. Pohli ◽  
A. Gottschalk ◽  
W. Gsell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alcohol Consumption ◽  
Chronic Alcohol ◽  
Chronic Alcohol Consumption
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