Iron as a therapeutic target in chronic liver disease

Tsomidis, Ioannis; Voumvouraki, Argyro

doi:10.3748/wjg.v29.i4.616

Cited by 13 publications

(5 citation statements)

References 544 publications

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“…The downregulation of these genes may potentially be explained by a loss or dysfunction of hepatocytes in the context of iron overload. High iron can result in the death of primary hepatocytes, and iron overload in humans and rodents is linked to hepatocyte death and liver injury, with high iron also exacerbating liver injury induced by other toxins and disease (Chen, Sugiyama et al 2020;Kouroumalis, Tsomidis et al 2023). Death occurs by a variety of mechanisms including apoptosis, necrosis, and, as more recently reported, ferroptosis (Zhao, Laissue et al 1997;Hassannia, Vandenabeele et al 2019;Wu, Wang et al 2021).…”

Section: Discussionmentioning

confidence: 99%

The Genetic Architecture of Dietary Iron Overload and Associated Pathology in Mice

Fuqua,

Moses,

McLachlan

et al. 2023

Preprint

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Tissue iron overload is a frequent pathologic finding in multiple disease states including non-alcoholic fatty liver disease (NAFLD), neurodegenerative disorders, cardiomyopathy, diabetes, and some forms of cancer. The role of iron, as a cause or consequence of disease progression and observed phenotypic manifestations, remains controversial. In addition, the impact of genetic variation on iron overload related phenotypes is unclear, and the identification of genetic modifiers is incomplete. Here, we used the Hybrid Mouse Diversity Panel (HMDP), consisting of over 100 genetically distinct mouse strains optimized for genome-wide association studies and systems genetics, to characterize the genetic architecture of dietary iron overload and pathology. Dietary iron overload was induced by feeding male mice (114 strains, 6-7 mice per strain on average) a high iron diet for six weeks, and then tissues were collected at 10-11 weeks of age. Liver metal levels and gene expression were measured by ICP-MS/ICP-AES and RNASeq, and lipids were measured by colorimetric assays. FaST-LMM was used for genetic mapping, and Metascape, WGCNA, and Mergeomics were used for pathway, module, and key driver bioinformatics analyses. Mice on the high iron diet accumulated iron in the liver, with a 6.5 fold difference across strain means. The iron loaded diet also led to a spectrum of copper deficiency and anemia, with liver copper levels highly positively correlated with red blood cell count, hemoglobin, and hematocrit. Hepatic steatosis of various severity was observed histologically, with 52.5 fold variation in triglyceride levels across the strains. Liver triglyceride and iron mapped most significantly to an overlapping locus on chromosome 7 that has not been previously associated with either trait. Based on network modeling, significant key drivers for both iron and triglyceride accumulation are involved in cholesterol biosynthesis and oxidative stress management. To make the full data set accessible and useable by others, we have made our data and analyses available on a resource website.

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Section: Discussionmentioning

confidence: 99%

The Genetic Architecture of Dietary Iron Overload and Associated Pathology in Mice

Fuqua,

Moses,

McLachlan

et al. 2023

Preprint

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“…WJG v29i4: For this issue, I like the following papers: (1) Chronic liver disease: “Iron as a therapeutic target in chronic liver disease”[ 11 ]. However, the number of references is excessive; and (2) Ulcerative colitis: “Gaseous metabolites as therapeutic targets in ulcerative colitis”[ 12 ].…”

Section: Hot Articles and Insufficient Articlesmentioning

confidence: 99%

Editor-in-Chief articles of choice and comments at the year-end of 2023

Tarnawski

2024

World J Gastroenterol

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As the Editor-in-Chief, every week prior to a new issue’s online publication, I perform a careful review of all encompassed articles, including the title, clinical and/or research importance, originality, novelty, and ratings by the peer reviewers. Based on this review, I select the papers of choice and suggest pertinent changes (e.g. , in the title) to the Company Editors responsible for publication. This process, while time-consuming, is very important for assuring the quality of publications and highlighting important articles that Readers may revisit.

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“…Generally, plasma iron is mainly absorbed in the form of divalent iron (Fe 2+ ) in duodenal enterocytes 12 . Divalent iron is oxidized into trivalent iron by ceruloplasmin and then transported to various tissues and cells bound to transferrin 13 . Inorganic trivalent iron (Fe 3+ ) accompanied by transferrin binds to transferrin receptor 1 (TFR1) on the cellular membrane 14 and is subsequently released into the cytoplasm 15 .…”

Section: Mechanism Of Ferroptosismentioning

confidence: 99%

Current Progress of Ferroptosis Study in Hepatocellular Carcinoma

Zhu,

Sha,

Zang

et al. 2024

Int. J. Biol. Sci.

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Ferroptosis, an emerging type of programmed cell death, is initiated by iron-dependent and excessive ROS-mediated lipid peroxidation, which eventually leads to plasma membrane rupture and cell death. Many canonical signalling pathways and biological processes are involved in ferroptosis. Furthermore, cancer cells are more susceptible to ferroptosis due to the high load of ROS and unique metabolic characteristics, including iron requirements. Recent investigations have revealed that ferroptosis plays a crucial role in the progression of tumours, especially HCC. Specifically, the induction of ferroptosis can not only inhibit the growth of hepatoma cells, thereby reversing tumorigenesis, but also improves the efficacy of immunotherapy and enhances the antitumour immune response. Therefore, triggering ferroptosis has become a new therapeutic strategy for cancer therapy. In this review, we summarize the characteristics of ferroptosis based on its underlying mechanism and role in HCC and provide possible therapeutic applications.

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Iron as a therapeutic target in chronic liver disease

Cited by 13 publications

References 544 publications

The Genetic Architecture of Dietary Iron Overload and Associated Pathology in Mice

The Genetic Architecture of Dietary Iron Overload and Associated Pathology in Mice

Editor-in-Chief articles of choice and comments at the year-end of 2023

Current Progress of Ferroptosis Study in Hepatocellular Carcinoma

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