Mechanistic Modelling of Drug-Induced Liver Injury: Investigating the Role of Innate Immune Responses.

Autor: Shoda LK; DILIsym Services, Inc., Research Triangle Park, NC, USA., Battista C; DILIsym Services, Inc., Research Triangle Park, NC, USA.; UNC Institute for Drug Safety Sciences, University of North Carolina at Chapel Hill, Research Triangle Park, NC, USA., Siler SQ; DILIsym Services, Inc., Research Triangle Park, NC, USA., Pisetsky DS; Medical Research Service, Durham VA Medical Center and Duke University Medical Center, Durham, NC, USA., Watkins PB; UNC Institute for Drug Safety Sciences, University of North Carolina at Chapel Hill, Research Triangle Park, NC, USA., Howell BA; DILIsym Services, Inc., Research Triangle Park, NC, USA.
Jazyk: angličtina
Zdroj: Gene regulation and systems biology [Gene Regul Syst Bio] 2017 May 30; Vol. 11, pp. 1177625017696074. Date of Electronic Publication: 2017 May 30 (Print Publication: 2017).
DOI: 10.1177/1177625017696074
Abstrakt: Drug-induced liver injury (DILI) remains an adverse event of significant concern for drug development and marketed drugs, and the field would benefit from better tools to identify liver liabilities early in development and/or to mitigate potential DILI risk in otherwise promising drugs. DILIsym software takes a quantitative systems toxicology approach to represent DILI in pre-clinical species and in humans for the mechanistic investigation of liver toxicity. In addition to multiple intrinsic mechanisms of hepatocyte toxicity (ie, oxidative stress, bile acid accumulation, mitochondrial dysfunction), DILIsym includes the interaction between hepatocytes and cells of the innate immune response in the amplification of liver injury and in liver regeneration. The representation of innate immune responses, detailed here, consolidates much of the available data on the innate immune response in DILI within a single framework and affords the opportunity to systematically investigate the contribution of the innate response to DILI.
Competing Interests: DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosures and Ethics As a requirement of publication author(s) have provided to the publisher signed confirmation of compliance with legal and ethical obligations including but not limited to the following: authorship and contributorship, conflicts of interest, privacy and confidentiality and (where applicable) protection of human and animal research subjects. The authors have read and confirmed their agreement with the ICMJE authorship and conflict of interest criteria. The authors have also confirmed that this article is unique and not under consideration or published in any other publication, and that they have permission from rights holders to reproduce any copyrighted material. Any disclosures are made in this section. The external blind peer reviewers report no conflicts of interest.
Databáze: MEDLINE
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