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Journal ArticleDOI

Oxidative Stress as a Critical Factor in Nonalcoholic Fatty Liver Disease Pathogenesis

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TLDR
Although augmented concentrations of ROS and faulty antioxidant defense have been associated to NAFLD and related complications, mechanisms of action and proofs of principle should be highlighted to support the causative role of OxS and to translate its concept into the clinic.
Abstract
Significance: Nonalcoholic fatty liver disease (NAFLD), characterized by liver triacylglycerol build-up, has been growing in the global world in concert with the raised prevalence of cardiometabolic disorders, including obesity, diabetes, and hyperlipemia. Redox imbalance has been suggested to be highly relevant to NAFLD pathogenesis. Recent Advances: As a major health problem, NAFLD progresses to the more severe nonalcoholic steatohepatitis (NASH) condition and predisposes susceptible individuals to liver and cardiovascular disease. Although NAFLD represents the predominant cause of chronic liver disorders, the mechanisms of its development and progression remain incompletely understood, even if various scientific groups ascribed them to the occurrence of insulin resistance, dyslipidemia, inflammation, and apoptosis. Nevertheless, oxidative stress (OxS) more and more appears as the most important pathological event during NAFLD development and the hallmark between simple steatosis and NASH manif...

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Journal ArticleDOI

Mitochondrial electron transport chain, ROS generation and uncoupling (Review)

TL;DR: This review discusses the sites of ROS generation in each ETC complex, including sites IF and IQ in complex I, site IIF in complex II and site IIIQo in complex III, and the physiological and pathological regulation of ROS.
Journal ArticleDOI

Molecular pathways of nonalcoholic fatty liver disease development and progression

TL;DR: This review is aimed at integrating the overwhelming progress made in the characterization of the physiopathological mechanisms of NAFLD at a molecular level, to better understand the factor influencing the initiation and progression of the disease.
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Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?

TL;DR: This review provides succinct insights into the molecular mechanisms responsible for lipotoxicity in NAFLD, including ER and oxidative stress, autophagy, lipoapotosis and inflammation, and highlights the role of CD36/FAT fatty acid translocase inNAFLD pathogenesis.
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Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway.

TL;DR: Fructose-induced miR-200a low-expression increased Keap1 to block Nrf2 antioxidant pathway, and then enhanced ROS-driven TXNIP to activate NLRP3 inflammasome and disturb lipid metabolism-related proteins, causing inflammation and lipid deposition in BRL-3A cells is demonstrated.
Journal ArticleDOI

Therapeutic Landscape for NAFLD in 2020

TL;DR: The treatment landscape in this rapidly evolving field with an emphasis on drugs in Phase 2 and Phase 3 trials is reviewed, likely that patients develop the phenotype of NASH by multiple mechanisms and thus the optimal treatments ofNASH will likely evolve to personalized therapy once the authors understand the mechanistic underpinnings of NASh in each patient.
References
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Journal ArticleDOI

Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations

TL;DR: The presence of C282Y mutations in patients with NAFLD is associated with greater HC iron deposition and decreased serum hepcidin levels, and there is a positive relationship between hepatic iron stores and serum hePCidin level across all HFE genotypes.
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Association of genetic polymorphisms of glutathione-S-transferase genes (GSTT1, GSTM1, and GSTP1) and susceptibility to nonalcoholic fatty liver disease in Zahedan, Southeast Iran.

TL;DR: This study showed that GSTM1 and GSTP1, but not GSTT1, genetic polymorphisms are associated with NAFLD in a sample of the Iranian population, and may be used to determine the risk of development ofNAFLD.
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Levels of the Oxidative Stress Marker γ-Glutamyltranspeptidase at Different Stages of Nonalcoholic Fatty Liver Disease

TL;DR: Levels of GGT in fatty liver patients may compensate for mild oxidative stress by repressing 8-OHdG levels and preventing progression to NASH; however further oxidative stress leads to increased levels of 8- OHdG and the development of NASH.
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Silymarin for HCV infection

TL;DR: The current state of knowledge on silymarin in the context of HCV infection is summarized from a recent workshop on silibinin in Germany.
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Dietary Fructose Activates Insulin Signaling and Inflammation in Adipose Tissue: Modulatory Role of Resveratrol.

TL;DR: Resveratrol supplementation markedly restored the levels of MDA, IL6, IL-10, and IL-18, as well as iNOS, Nrf2, and PI3K mRNA, in adipose tissues of both genders, proposing no correlation between the tissue insulin signaling and inflammation.
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