Ferroptosis is involved in alcohol-induced cell death <i>in vivo</i> and <i>in vitro</i>

Liu, Chunyu; Wang, Min; Yu, Hao; Han, Fangxuan; Wu, Qiong-Shi; Cai, Xingjun; Kojima, Hiroshi; Chen, Yongxing; Li, Yi-Fang; He, Rong‐Rong

doi:10.1080/09168451.2020.1763155

Cited by 64 publications

(35 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although there is a growing consensus that lipid disorder and hepatic iron overload are prevalent features of ALD [ 72 ], only in recent years have researchers began taking ferroptosis’ role in alcoholic liver damage into consideration. During the repair of ethanol-induced liver damage, ferroptosis is always negatively regulated [ 73 , 74 ]. Alcohol treatment results in massive ROS accumulation and lipid peroxidation both in cell culture and in mouse models of ALD, which could be rescued by a ferroptosis inhibitor [ 74 ].…”

Section: The Involvement Of Ferroptosis In Typical Liver Diseasesmentioning

confidence: 99%

“…During the repair of ethanol-induced liver damage, ferroptosis is always negatively regulated [ 73 , 74 ]. Alcohol treatment results in massive ROS accumulation and lipid peroxidation both in cell culture and in mouse models of ALD, which could be rescued by a ferroptosis inhibitor [ 74 ]. Similarly, some investigations found that dimethyl fumarate has a protective effect on ethanol-induced oxidative injury through activating the Nrf2 pathway and repressing ferroptosis [ 73 ].…”

Section: The Involvement Of Ferroptosis In Typical Liver Diseasesmentioning

confidence: 99%

“…(VI) In chronic liver disease (e.g., ALD, NAFLD), ferroptosis is primarily responsible for liver damage, and inhibiting ferroptosis would reverse the deleterious effect. However, in HCC, ferroptosis could increase cell sensitivity to sorafenib, and inhibiting this cell death contributes to drug resistance [ 54 , 74 , 85 ]. Generally, chronic liver injury and repair would end up with fibrosis and even HCC.…”

Section: Challenges and Future Directionsmentioning

confidence: 99%

See 2 more Smart Citations

Ferroptosis in liver disease: new insights into disease mechanisms

et al. 2021

View full text Add to dashboard Cite

Characterized by excessive iron accumulation and lipid peroxidation, ferroptosis is a novel form of iron-dependent cell death, which is morphologically, genetically, and biochemically distinct from other well-known cell death. In recent years, ferroptosis has been quickly gaining attention in the field of liver diseases, as the liver is predisposed to oxidative injury and generally, excessive iron accumulation is a primary characteristic of most major liver diseases. In the current review, we first delineate three cellular defense mechanisms against ferroptosis (GPx4 in the mitochondria and cytosol, FSP1 on plasma membrane, and DHODH in mitochondria), along with four canonical modulators of ferroptosis (system Xc−, nuclear factor erythroid 2-related factor 2, p53, and GTP cyclohydrolase-1). Next, we review recent progress of ferroptosis studies delineating molecular mechanisms underlying the pathophysiology of several common liver diseases including ischemia/reperfusion-related injury (IRI), nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), hemochromatosis (HH), drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). Furthermore, we also highlight both challenges and promises that emerged from recent studies that should be addressed and pursued in future investigations before ferroptosis regulation could be adopted as an effective therapeutic target in clinical practice.

show abstract

Section: The Involvement Of Ferroptosis In Typical Liver Diseasesmentioning

confidence: 99%

Section: The Involvement Of Ferroptosis In Typical Liver Diseasesmentioning

confidence: 99%

Section: Challenges and Future Directionsmentioning

confidence: 99%

See 1 more Smart Citation

Ferroptosis in liver disease: new insights into disease mechanisms

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Fer-1 is a recognized inhibitor of ferroptosis which can reduce PUFAs in membrane oxidation [ 8 ]. By inhibiting hepatocyte ferroptosis, Fer-1 improves liver damage mediated by ALD, NAFLD, and hepatic ischemia/reperfusion (I/R) injury [ 29 , 76 , 99 ] ( Table 1 ). With in-depth exploration of this field, recent research has solved the long-standing Fer-1 anti-ferroptosis paradox.…”

Section: Drugs Targeting Ferroptosis In Liver Diseasesmentioning

confidence: 99%

Role of Ferroptosis in Non-Alcoholic Fatty Liver Disease and Its Implications for Therapeutic Strategies

Zhang

2021

Biomedicines

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) has become the chronic liver disease with the highest incidence throughout the world, but its pathogenesis has not been fully elucidated. Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation. Abnormal iron metabolism, lipid peroxidation, and accumulation of polyunsaturated fatty acid phospholipids (PUFA-PLs) can all trigger ferroptosis. Emerging evidence indicates that ferroptosis plays a critical role in the pathological progression of NAFLD. Because the liver is the main organ for iron storage and lipid metabolism, ferroptosis is an ideal target for liver diseases. Inhibiting ferroptosis may become a new therapeutic strategy for the treatment of NAFLD. In this article, we describe the role of ferroptosis in the progression of NAFLD and its related mechanisms. This review will highlight further directions for the treatment of NAFLD and the selection of corresponding drugs that target ferroptosis.

show abstract

“…A second parallel protective pathway also exist, which involves the oxidoreductase FSP1/AIFM2 by generating a potent lipophilic antioxidant to suppresses the propagation of lipid peroxides (63,64). Hepatic ferroptosis has been found in the liver of animal models of alcoholic liver disease (ALD), nonalcoholic steatohepatitis, acetaminophen induced hepatotoxicity, and viral hepatitis (65)(66)(67)(68). However, it remains to be determined whether bile acids cause hepatocyte ferroptosis during cholestasis.…”

Section: Cholestatic Levels Of Bile Acids Injure Hepatocytesmentioning

confidence: 99%

The role of bile acids in cholestatic liver injury

Cai¹,

Boyer²

2021

Ann Transl Med

View full text Add to dashboard Cite

Clinical disorders that impair bile flow result in retention of bile acids and cholestatic liver injury, characterized by parenchymal cell death, bile duct proliferation, liver inflammation and fibrosis. However, the pathogenic role of bile acids in the development of cholestatic liver injury remains incompletely understood.In this review, we summarize the current understanding of this process focusing on the experimental and clinical evidence for direct effects of bile acids on each major cellular component of the liver: hepatocytes, cholangiocytes, stellate cells and immune cells. During cholestasis bile acids accumulated in the liver, causing oxidative stress and mitochondrial injury in hepatocytes. The stressed hepatocytes respond by releasing inflammatory cytokines through activation of specific signaling pathways and transcription factors. The recruited neutrophils and other immune cells then cause parenchymal cell death. In addition, bile acids also stimulate the proliferation of cholangiocytes and stellate cells that are responsible for bile duct proliferation and liver fibrosis. This review explores the evidence for bile acid involvement in these phenomena. The role of bile acid receptors, TGR5, FXR and the sphingosine-1-phosphate receptor 2 and the inflammasome are also examined. We hope that better understanding of these pathologic effects will facilitate new strategies for treating cholestatic liver injury.

show abstract

Ferroptosis is involved in alcohol-induced cell death in vivo and in vitro

Cited by 64 publications

References 43 publications

Ferroptosis in liver disease: new insights into disease mechanisms

Ferroptosis in liver disease: new insights into disease mechanisms

Role of Ferroptosis in Non-Alcoholic Fatty Liver Disease and Its Implications for Therapeutic Strategies

The role of bile acids in cholestatic liver injury

Contact Info

Product

Resources

About