Acetaminophen induced acute liver failure via oxidative stress and JNK activation: Protective role of taurine by the suppression of cytochrome P450 2E1

2010 ◽  
Vol 44 (3) ◽  
pp. 340-355 ◽  
Author(s):  
Joydeep Das ◽  
Jyotirmoy Ghosh ◽  
Prasenjit Manna ◽  
Parames C. Sil
Keyword(s):  
Oxidative Stress ◽  
Cytochrome P450 ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Protective Role ◽  
Cytochrome P450 2E1 ◽  
Jnk Activation

scholarly journals The role of cytochrome P450 2E1 on ethanol-mediated oxidative stress and HIV replication in human monocyte-derived macrophages

2019 ◽  
Vol 17 ◽  
pp. 65-70 ◽  
Author(s):  
Yuqing Gong ◽  
P.S.S. Rao ◽  
Namita Sinha ◽  
Sabina Ranjit ◽  
Theodore J. Cory ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cytochrome P450 ◽  
Human Monocyte ◽  
Cytochrome P450 2E1 ◽  
Hiv Replication

scholarly journals Role of Mitochondrial Cytochrome P450 2E1 in Healthy and Diseased Liver

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 288
Author(s):  
Julie Massart ◽  
Karima Begriche ◽  
Jessica H. Hartman ◽  
Bernard Fromenty
Keyword(s):  
Oxidative Stress ◽  
Cytochrome P450 ◽  
Liver Disease ◽  
Fatty Liver ◽  
Current Knowledge ◽  
Physiological Role ◽  
Experimental Investigations ◽  
Rat Liver Mitochondria ◽  
Cytochrome P450 2E1

Cytochrome P450 2E1 (CYP2E1) is pivotal in hepatotoxicity induced by alcohol abuse and different xenobiotics. In this setting, CYP2E1 generates reactive metabolites inducing oxidative stress, mitochondrial dysfunction and cell death. In addition, this enzyme appears to play a role in the progression of obesity-related fatty liver to nonalcoholic steatohepatitis. Indeed, increased CYP2E1 activity in nonalcoholic fatty liver disease (NAFLD) is deemed to induce reactive oxygen species overproduction, which in turn triggers oxidative stress, necroinflammation and fibrosis. In 1997, Avadhani’s group reported for the first time the presence of CYP2E1 in rat liver mitochondria, and subsequent investigations by other groups confirmed that mitochondrial CYP2E1 (mtCYP2E1) could be found in different experimental models. In this review, we first recall the main features of CYP2E1 including its role in the biotransformation of endogenous and exogenous molecules, the regulation of its expression and activity and its involvement in different liver diseases. Then, we present the current knowledge on the physiological role of mtCYP2E1, its contribution to xenobiotic biotransformation as well as the mechanism and regulation of CYP2E1 targeting to mitochondria. Finally, we discuss experimental investigations suggesting that mtCYP2E1 could have a role in alcohol-associated liver disease, xenobiotic-induced hepatotoxicity and NAFLD.

Protective role of AGK2 on thioacetamide-induced acute liver failure in mice

Life Sciences ◽  
2019 ◽  
Vol 230 ◽  
pp. 68-75 ◽  
Author(s):  
Fang-Zhou Jiao ◽  
Yao Wang ◽  
Wen-Bin Zhang ◽  
Hai-Yue Zhang ◽  
Qian Chen ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Protective Role

ORY supplementation mitigates acetaminophen-induced acute liver failure in male mice: role of oxidative stress and apoptotic markers

2020 ◽  
Vol 393 (11) ◽  
pp. 2129-2137
Author(s):  
Marcelo Gomes de Gomes ◽  
Lucian Del Fabbro ◽  
André Rossito Goes ◽  
Leandro Cattelan Souza ◽  
Silvana Peterini Boeira ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Male Mice ◽  
Apoptotic Markers

scholarly journals Protective Role of 4-Octyl Itaconate in Murine LPS/D-GalN-Induced Acute Liver Failure via Inhibiting Inflammation, Oxidative Stress, and Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Ruidong Li ◽  
Wenchang Yang ◽  
Yuping Yin ◽  
Peng Zhang ◽  
Yaxin Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Murine Model ◽  
Nuclear Translocation ◽  
Thiobarbituric Acid ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Ros Generation ◽  
Related Factor

Oxidative stress, inflammation, and apoptosis are crucial in the pathogenesis of acute liver failure (ALF). 4-Octyl itaconate (OI) showed antioxidative and anti-inflammatory properties in many disease models. However, its role in lipopolysaccharide- (LPS-)/D-galactosamine- (D-GalN-) induced ALF is still not investigated. Here, we established an ALF murine model induced by LPS/D-GalN administration. And we found that OI improved survival rate in the murine ALF model. Our results also showed that OI alleviated LPS/D-GalN-induced hepatic histopathological injury and reduced the serum activities of alanine transaminase and aspartate transaminase. Moreover, OI reduced serum levels of proinflammatory cytokines such as monocyte chemotactic protein-1, tumor necrosis factors-α, and interlukin-6. Additionally, OI mitigated oxidative stress and alleviated lipid peroxidation in a murine model of ALF. This was evaluated by a reduction of thiobarbituric acid reactive substances (TBARS) in liver tissues. In addition, OI increased the ratio of reduced glutathione/oxidized glutathione and the activities of antioxidant enzymes including catalase and superoxide dismutase. Moreover, the apoptosis of hepatocytes in the liver was inhibited by OI. Furthermore, we found that OI inhibited LPS-induced nuclear translocation and activation of factor-kappa B (NF-κB) p65 in macrophages which could be inhibited by OI-induced activation of nuclear factor erythroid-2-related factor (Nrf2) signaling. Additionally, D-GalN-induced reactive oxygen species (ROS) generation and apoptosis in hepatocytes were inhibited by OI-induced activation of Nrf2 signaling. Therefore, the underlying mechanism for OI’s protective effect in LPS/D-GalN-induced ALF may be associated with deactivation of NF-κB signaling in macrophages to reduce inflammation and inhibition of ROS-related hepatocyte apoptosis by activating Nrf2. In conclusion, OI showed a protective role in LPS/D-GalN-induced ALF by reducing inflammation, enhancing antioxidant capacity, and inhibiting cell apoptosis.

scholarly journals Protective role of hypoxia-inducible factor-1α-dependent CD39 and CD73 in fulminant acute liver failure

2017 ◽  
Vol 314 ◽  
pp. 72-81 ◽  
Author(s):  
Eunyoung Tak ◽  
Dong-Hwan Jung ◽  
Seok-Hwan Kim ◽  
Gil-Chun Park ◽  
Dae Young Jun ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Hypoxia Inducible Factor ◽  
Protective Role ◽  
Hypoxia Inducible Factor 1Α

scholarly journals Noncanonical Wnt5a/JNK Signaling Contributes to the Development of D-Gal/LPS-Induced Acute Liver Failure

2021 ◽  
Author(s):  
Xiang-fen Ji ◽  
Yu-chen Fan ◽  
Fei Sun ◽  
Jing-wei Wang ◽  
kai wang
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Inflammatory Cytokines ◽  
Dependent Manner ◽  
Jnk Signaling ◽  
Wnt5a Expression ◽  
Jnk Activation

Abstract Acute liver failure (ALF) is a deadly clinical disorder with few effective treatments and unclear pathogenesis. In our previous study, we demonstrated that aberrant Wnt5a expression was involved in acute on chronic liver failure. However, the role of Wnt5a in ALF is unknown. We investigated the expression of Wnt5a and its downstream signaling of c-jun N-terminal kinase (JNK) in a mouse model of ALF established by co-injection of D-galactosamine (D-Gal) and lipopolysaccharide (LPS) in C57BL/6 mice. We also investigated the role of Box5, a Wnt5a antagonist in vivo. Moreover, the effect of Wnt5a/JNK signaling on downstream inflammatory cytokines expression, phagocytosis and migration in THP-1 macrophages was studied in vitro. Aberrant Wnt5a expression and JNK activation were detected in D-Gal/LPS-induced ALF mice. Box5 pretreatment reversed JNK activation, and eventually decreased the mortality rate of D-Gal/LPS-treated mice with reduced hepatic necrosis and apoptosis, serum ALT and AST levels, and liver inflammatory cytokines expression, although the last was not significant. We further demonstrated that recombined Wnt5a (rWnt5a) induced tumor necrosis α (TNF-α) and Interleukin-6 (IL-6) mRNA expression, and increased the phagocytosis ability of THP-1 macrophages in a JNK-dependent manner, which could be restored by Box5. In addition, rWnt5a-induced migration of THP-1 macrophages was also turned by Box5. Our findings suggested that Wnt5a/JNK signaling play important role in the development of ALF, and Box5 could have particular hepatoprotecive effects in ALF.

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