scholarly journals Baicalin Ameliorates Liver Injury Induced by Chronic plus Binge Ethanol Feeding by Modulating Oxidative Stress and Inflammation via CYP2E1 and NRF2 in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Ping He ◽  
Yafeng Wu ◽  
Jianchao Shun ◽  
Yaodong Liang ◽  
Mingliang Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Transcription Factor ◽  
Liver Injury ◽  
Cell Activation ◽  
Antioxidant Defense ◽  
Defense Mechanism ◽  
Nuclear Translocation ◽  
Transcriptional Level ◽  
Binge Ethanol

Alcoholic liver injury leads to serious complication including death. The potential role of baicalin at the transcription level in mice model of alcohol injury is not known yet. In this study, we examined the effect of baicalin against chronic plus binge ethanol model in mice and understanding the mechanism of protection. Liver function, histology, steatosis, inflammation, NF-κB activity, oxidative stress sources, nuclear translocation of NRF2 transcription factor, and cell death were assessed. Treatment with baicalin ameliorated ethanol-induced oxidative stress, inflammation, and cell death. Baicalin attenuated ethanol-induced proinflammatory molecules such as TNF-α, IL-1β, MIP-2, and MCP-1 and reversed redox-sensitive transcription factor NF-κB activation. Baicalin also modulated Kupffer cell activation in vitro. Baicalin inhibited ethanol-induced expression of reactive oxygen species (ROS) generating enzymes NOX2, p67phox, xanthine oxidase, and iNOS in addition to CYP2E1 activities. Baicalin also enhanced ethanol-induced NRF2 nuclear translocation and increased downstream target gene HO-1 as antioxidant defense. Finally, baicalin reduced significant apoptotic and necrotic cell death. Our study suggests that baicalin ameliorates chronic plus binge ethanol-induced liver injury involving molecular crosstalk of multiple pathways at the transcriptional level and through upregulation of antioxidant defense mechanism.

scholarly journals Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Kezhen Shen ◽  
Xiaowen Feng ◽  
Hao Pan ◽  
Feng Zhang ◽  
Haiyang Xie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cell Death ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Cell Activation ◽  
Nuclear Translocation ◽  
Stellate Cell ◽  
Tissue Growth ◽  
Duct Ligation

Experimental cholestatic liver fibrosis was performed by bile duct ligation (BDL) in mice, and significant liver injury was observed in 15 days. Administration of baicalin in mice significantly ameliorates liver fibrosis. Experimental cholestatic liver fibrosis was associated with induced gene expression of fibrotic markers such as collagen I, fibronectin, alpha smooth muscle actin (SMA), and connective tissue growth factor (CTGF); increased inflammatory cytokines (TNFα, MIP1α, IL1β, and MIP2); increased oxidative stress and reactive oxygen species- (ROS-) inducing enzymes (NOX2 and iNOS); dysfunctional mitochondrial electron chain complexes; and apoptotic/necrotic cell death markers (DNA fragmentation, caspase 3 activity, and PARP activity). Baicalin administration on alternate day reduced fibrosis along with profibrotic gene expression, proinflammatory cytokines, oxidative stress, and cell death whereas improving the function of mitochondrial electron transport chain. We observed baicalin enhanced NRF2 activation by nuclear translocation and induced its target genes HO-1 and GCLM, thus enhancing antioxidant defense. Interplay of oxidative stress/inflammation and NRF2 were key players for baicalin-mediated protection. Stellate cell activation is crucial for initiation of fibrosis. Baicalin alleviated stellate cell activation and modulated TIMP1, SMA, collagen 1, and fibronectin in vitro. This study indicates that baicalin might be beneficial for reducing inflammation and fibrosis in liver injury models.

scholarly journals Enzyme-Treated Zizania latifolia Extract Protects against Alcohol-Induced Liver Injury by Regulating the NRF2 Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 960
Author(s):  
Bo Yoon Chang ◽  
Hyung Joong Kim ◽  
Tae Young Kim ◽  
Sung Yeon Kim
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Alcoholic Liver Disease ◽  
Antioxidant Defense ◽  
Defense Mechanism ◽  
Nuclear Translocation ◽  
Histopathological Examination ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Control Group

Binge drinking patterns easily produce a state of oxidative stress that disturbs liver function. Eventually, this leads to alcoholic liver disease. A safe and effective therapy for alcoholic liver disease remains elusive. Enzyme-treated Z. latifolia extract (ETZL) was studied as a potential agent for treating alcohol-induced liver disease. In addition, its underlying mechanisms were elucidated. In the binge model, ETZL was pretreated with alcohol (5 g/kg) three times at 12-h intervals. Our results showed that ETZL pretreatment decreased the serum levels of ALT, AST, ALP, and TG. ETZL treatment appeared to prevent an increase in hepatic TG and MDA levels, and there was a decrease in total GSH following alcohol treatment. Histopathological examination showed that lipid droplets were significantly reduced in the ETZL group compared to the control group. ETZL also exhibited radical scavenging activity. It significantly reduced t-BHP-induced cytotoxicity and the production of reactive oxygen species (ROS) in HepG2 cells. ETZL also enhanced NRF2 nuclear translocation and increased expression of the downstream target genes HO-1, NQO1, and GCLC as an antioxidant defense. Finally, ETZL treatment significantly reduced cell death. Our study suggests that ETZL ameliorates binge ethanol-induced liver injury by upregulating the antioxidant defense mechanism.

scholarly journals Spermidine Prevents Ethanol and Lipopolysaccharide-Induced Hepatic Injury in Mice

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1786
Author(s):  
Raghabendra Adhikari ◽  
Ruchi Shah ◽  
Karina Reyes-Gordillo ◽  
Jaime Arellanes-Robledo ◽  
Ying Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Liver Injury ◽  
Cell Activation ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Stellate Cell ◽  
Nuclear Factor Κb ◽  
Inhibitory Protein ◽  
Anti Inflammatory

To date, there is no effective treatment for alcoholic liver disease, despite its prevalence world-wide. Because alcohol consumption is associated with oxidative stress-induced liver injury and pro-inflammatory responses, naturally occurring antioxidants and/or anti-inflammatories may be potential therapeutics. Spermidine is an abundant, ubiquitous polyamine that has been found to display strong antioxidant and anti-inflammatory properties. To further investigate whether spermidine is an effective intervention for alcohol-induced liver disease, we examined its hepatoprotective properties using a two-hit, chronic ethanol and acute lipopolysaccharide (LPS)-induced mouse model of liver injury. We determined that spermidine administration prevented ethanol and LPS-induced increases in liver injury using plasma ALT as a readout. Furthermore, histological analysis of tissue from control and treated animals revealed that the pathology associated with ethanol and LPS treatment was prevented in mice additionally treated with spermidine. As predicted, spermidine also prevented ethanol and LPS-induced oxidative stress by decreasing the levels of both reactive oxygen species (ROS) and lipid peroxidation. We further determined that spermidine treatment prevented the nuclear translocation of nuclear factor κB (NFκB) by blocking the phosphorylation of the inhibitory protein, IκB, thereby preventing expression of pro-inflammatory cytokines. Finally, by measuring expression of known markers of hepatic stellate cell activation and monitoring collagen deposition, we observed that spermidine also prevented alcohol and LPS-induced hepatic fibrosis. Together, our results indicate that spermidine is an antioxidant thereby conferring anti-inflammatory and anti-fibrotic effects associated with alcoholic liver injury.

scholarly journals Protective Effect of Osmundacetone against Neurological Cell Death Caused by Oxidative Glutamate Toxicity

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 328
Author(s):  
Tuy An Trinh ◽  
Young Hye Seo ◽  
Sungyoul Choi ◽  
Jun Lee ◽  
Ki Sung Kang
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Defense Mechanism ◽  
Neuroprotective Effect ◽  
Glutamate Release ◽  
Chromatin Condensation ◽  
Critical Role ◽  
Glutamate Toxicity ◽  
Heme Oxygenase 1 ◽  
Brain Functions

Oxidative stress is one of the main causes of brain cell death in neurological disorders. The use of natural antioxidants to maintain redox homeostasis contributes to alleviating neurodegeneration. Glutamate is an excitatory neurotransmitter that plays a critical role in many brain functions. However, excessive glutamate release induces excitotoxicity and oxidative stress, leading to programmed cell death. Our study aimed to evaluate the effect of osmundacetone (OAC), isolated from Elsholtzia ciliata (Thunb.) Hylander, against glutamate-induced oxidative toxicity in HT22 hippocampal cells. The effect of OAC treatment on excess reactive oxygen species (ROS), intracellular calcium levels, chromatin condensation, apoptosis, and the expression level of oxidative stress-related proteins was evaluated. OAC showed a neuroprotective effect against glutamate toxicity at a concentration of 2 μM. By diminishing the accumulation of ROS, as well as stimulating the expression of heat shock protein 70 (HSP70) and heme oxygenase-1 (HO-1), OAC triggered the self-defense mechanism in neuronal cells. The anti-apoptotic effect of OAC was demonstrated through its inhibition of chromatin condensation, calcium accumulation, and reduction of apoptotic cells. OAC significantly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 kinases. Thus, OAC could be a potential agent for supportive treatment of neurodegenerative diseases.

scholarly journals Transcription factor NRF2 protects mice against dietary iron-induced liver injury by preventing hepatocytic cell death

2014 ◽  
Vol 60 (2) ◽  
pp. 354-361 ◽  
Author(s):  
Sandro Silva-Gomes ◽  
Ana G. Santos ◽  
Carolina Caldas ◽  
Cátia M. Silva ◽  
João V. Neves ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcription Factor ◽  
Liver Injury ◽  
Dietary Iron

Mechanisms of Liver Injury. III. Oxidative stress in the pathogenesis of hepatitis C virus

2006 ◽  
Vol 290 (5) ◽  
pp. G847-G851 ◽  
Author(s):  
Jinah Choi ◽  
J.-H. James Ou
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Injury ◽  
Iron Overload ◽  
Antioxidant Defense ◽  
Hcv Infection ◽  
Nitrogen Species ◽  
Systemic Oxidative Stress

Hepatitis C virus (HCV) is a major cause of viral hepatitis that can progress to hepatic fibrosis, steatosis, hepatocellular carcinoma, and liver failure. HCV infection is characterized by a systemic oxidative stress that is most likely caused by a combination of chronic inflammation, iron overload, liver damage, and proteins encoded by HCV. The increased generation of reactive oxygen and nitrogen species, together with the decreased antioxidant defense, promotes the development and progression of hepatic and extrahepatic complications of HCV infection. This review discusses the possible mechanisms of HCV-induced oxidative stress and its role in HCV pathogenesis.

Oxidative Stress and Antioxidant Defense Mechanism in Glomerular Diseases

1997 ◽  
Vol 22 (1-2) ◽  
pp. 161-168 ◽  
Author(s):  
Sándor Túri ◽  
Ilona Németh ◽  
Attila Torkos ◽  
Levente Sághy ◽  
Ilona Varga ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Defense ◽  
Defense Mechanism ◽  
Glomerular Diseases
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