Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPARγ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease
Joint Authors
Al Sharif, Merilin
Alov, Petko
Pajeva, Ilza
Tsakovska, Ivanka
Vitcheva, Vessela
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-03-18
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Comprehensive understanding of the precise mode of action/adverse outcome pathway (MoA/AOP) of chemicals becomes a key step towards superseding the current repeated dose toxicity testing methodology with new generation predictive toxicology tools.
The description and characterization of the toxicological MoA leading to non-alcoholic fatty liver disease (NAFLD) are of specific interest, due to its increasing incidence in the modern society.
Growing evidence stresses on the PPARγ ligand-dependent dysregulation as a key molecular initiating event (MIE) for this adverse effect.
The aim of this work was to analyze and systematize the numerous scientific data about the steatogenic role of PPARγ.
Over 300 papers were ranked according to preliminary defined criteria and used as reliable and significant sources of data about the PPARγ-dependent prosteatotic MoA.
A detailed analysis was performed regarding proteins which PPARγ-mediated expression changes had been confirmed to be prosteatotic by most experimental evidence.
Two probable toxicological MoAs from PPARγ ligand binding to NAFLD were described according to the Organisation for Economic Cooperation and Development (OECD) concepts: (i) PPARγ activation in hepatocytes and (ii) PPARγ inhibition in adipocytes.
The possible events at different levels of biological organization starting from the MIE to the organ response and the connections between them were described in details.
American Psychological Association (APA)
Al Sharif, Merilin& Alov, Petko& Vitcheva, Vessela& Pajeva, Ilza& Tsakovska, Ivanka. 2014. Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPARγ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease. PPAR Research،Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-1047274
Modern Language Association (MLA)
Al Sharif, Merilin…[et al.]. Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPARγ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease. PPAR Research No. 2014 (2014), pp.1-13.
https://search.emarefa.net/detail/BIM-1047274
American Medical Association (AMA)
Al Sharif, Merilin& Alov, Petko& Vitcheva, Vessela& Pajeva, Ilza& Tsakovska, Ivanka. Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPARγ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease. PPAR Research. 2014. Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-1047274
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1047274