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The identification of nuclear receptors associated with hepatic steatosis to develop and extend adverse outcome pathways.

Mellor, CL and Steinmetz, FP and Cronin, MTD (2016) The identification of nuclear receptors associated with hepatic steatosis to develop and extend adverse outcome pathways. Critical Reviews in Toxicology, 46 (2). pp. 138-152. ISSN 1547-6898

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Abstract

The development of adverse outcome pathways (AOPs) is becoming a key component of twenty-first century toxicology. AOPs provide a conceptual framework that links the molecular initiating event to an adverse outcome through organized toxicological knowledge, bridging the gap from chemistry to toxicological effect. As nuclear receptors (NRs) play essential roles for many physiological processes within the body, they are used regularly as drug targets for therapies to treat many diseases including diabetes, cancer and neurodegenerative diseases. Due to the heightened development of NR ligands, there is increased need for the identification of related AOPs to facilitate their risk assessment. Many NR ligands have been linked specifically to steatosis. This article reviews and summarizes the role of NR and their importance with links between NR examined to identify plausible putative AOPs. The following NRs are shown to induce hepatic steatosis upon ligand binding: aryl hydrocarbon receptor, constitutive androstane receptor, oestrogen receptor, glucocorticoid receptor, farnesoid X receptor, liver X receptor, peroxisome proliferator-activated receptor, pregnane X receptor and the retinoic acid receptor. A preliminary, putative AOP was formed for NR binding linked to hepatic steatosis as the adverse outcome.

Item Type: Article
Additional Information: This is an Accepted Manuscript of an article published by Taylor & Francis in Critical Reviews in Toxicology on 9 Oct 2015, available online: http://wwww.tandfonline.com/10.3109/10408444.2015.1089471
Uncontrolled Keywords: 1115 Pharmacology And Pharmaceutical Sciences
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Taylor and Francis
Related URLs:
Date Deposited: 02 Feb 2016 11:59
Last Modified: 09 Oct 2016 23:50
DOI or Identification number: 10.3109/10408444.2015.1089471
URI: http://researchonline.ljmu.ac.uk/id/eprint/2678

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