Pharmacological Activation of Nrf2 Enhances Functional Liver Regeneration.
Benjamin K Y Chan,Mohamed Elmasry,Shiva S. Forootan,Giusy Russomanno,Tobias M Bunday,Fang Zhang,Nathalie Brillant,Philip J. Starkey Lewis,Rhona Aird,Emanuele Ricci,Timothy Andrews,Rowena Sison-Young,Amy Schofield,Yongxiang Fang,Adam Lister,Jack Sharkey,Harish Poptani,Neil R. Kitteringham,Stuart J. Forbes,Hassan Malik,Stephen W. Fenwick,B. Kevin Park,Christopher E. Goldring,Ian M. Copple +23 more
TLDR
In this paper, bardoxolone methyl (CDDO-Me), a potent activator of Nrf2 that has entered clinical development, was administered to wild-type and non-Nrf2 null mice and then subjected to two-thirds partial hepatectomy.About:
This article is published in Hepatology.The article was published on 2021-08-01 and is currently open access. It has received 13 citations till now. The article focuses on the topics: Liver regeneration & Liver function.read more
Citations
More filters
Journal ArticleDOI
Role of Oxidative Stress in Liver Disorders
Laura Conde de la Rosa,Leire Goicoechea,Sandra Torres,Carmen García-Ruiz,José C. Fernández-Checa +4 more
TL;DR: An overview of the sources and targets of ROS in different liver diseases and the pivotal role of oxidative stress in cell death is highlighted and current antioxidant therapies as treatment options for such disorders are discussed.
Journal ArticleDOI
Selective disruption of NRF2-KEAP1 interaction leads to NASH resolution and reduction of liver fibrosis in mice
Klaus Seedorf,Csaba Wéber,Cédric Vinson,Sylvie Berger,Laurent Vuillard,Árpád Kiss,Stéphanie Creusot,Olivier Broux,Anne Géant,Catherine Ilic,Karine Lemaitre,Johann Richard,Adel Hammoutene,Julien Mahieux,Virginie Martigny,Didier Durand,Fabien Melchiore,Miklós Nyerges,Valerie R. Paradis,Nicolas Provost,V Duvivier,Philippe Delerive +21 more
TL;DR: S217879 as discussed by the authors is a small molecule that could disrupt the KEAP1-NRF2 interaction, which is a major driver of non-alcoholic steatohepatitis (NASH) progression.
Journal ArticleDOI
Novel NRF2‐activated cancer treatments utilizing synthetic lethality
TL;DR: The mechanisms through which acquired NRF2 hyperactivation can result in resistance of tumours to immune checkpoint inhibitor therapies in addition to classical chemotherapeutics are discussed, and it is proposed that using a synthetic lethal strategy mediated byNRF2-target gene-dependent bioactivation of prodrugs represents a promising strategy to specifically enhance toxicity to heretofore untreatable NRF 2-hyperactivated human tumours.
Journal ArticleDOI
New Perspectives to Improve Mesenchymal Stem Cell Therapies for Drug-Induced Liver Injury
TL;DR: This concise review of the pathophysiology of DILI is focused on and new experimental approaches conceived to improve cell-based therapy by the in vitro preconditioning of MSCs and/or the use of cell-free products as treatment for this liver condition are highlighted.
Journal ArticleDOI
Redox experimental medicine and liver regeneration
TL;DR: Modulation of redox-dependent molecular pathways to enhance liver regeneration is even more intriguing, and preliminary studies focused on the identification of these targets will pave the way for viable therapies to be tested in clinical trials.
References
More filters
Journal ArticleDOI
An nrf2/small maf heterodimer mediates the induction of phase ii detoxifying enzyme genes through antioxidant response elements
Ken Itoh,Tomoki Chiba,Satoru Takahashi,Tetsuro Ishii,Kazuhiko Igarashi,Yasutake Katoh,Tatsuya Oyake,Norio Hayashi,Kimihiko Satoh,Ichiro Hatayama,Masayuki Yamamoto,Yo-ichi Nabeshima +11 more
TL;DR: It is demonstrated that Nrf2 is essential for the transcriptional induction of phase II enzymes and the presence of a coordinate transcriptional regulatory mechanism for phase II enzyme genes and the nrf2-deficient mice may prove to be a very useful model for the in vivo analysis of chemical carcinogenesis and resistance to anti-cancer drugs.
Journal ArticleDOI
Burden of liver diseases in the world
TL;DR: The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis.
Journal ArticleDOI
The Nrf2 regulatory network provides an interface between redox and intermediary metabolism
TL;DR: Observations suggest Nrf2 directs metabolic reprogramming during stress, which would enable the factor to orchestrate adaptive responses to diverse forms of stress.
Journal ArticleDOI
The KEAP1-NRF2 System: a Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis
TL;DR: This review describes historical milestones in the initial characterization of the KEAP1-NRF2 system and provides a comprehensive overview of the molecular mechanisms governing the functions ofKEAP1 and NRF2, as well as their roles in physiology and pathology.
Journal ArticleDOI
Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases
Antonio Cuadrado,Ana I. Rojo,Geoffrey Wells,John D. Hayes,Sharon P. Cousin,William L. Rumsey,Attucks Otis Clinton,Stephen Franklin,Anna-Liisa Levonen,Thomas W. Kensler,Albena T. Dinkova-Kostova,Albena T. Dinkova-Kostova +11 more
TL;DR: An overview of the physiological and pathological roles of NRF2 is provided, emerging pharmacological modulators of theNRF2–KEAP1 axis are presented and associated drug development challenges are highlighted.