期刊
TOXICOLOGY LETTERS
卷 280, 期 -, 页码 79-91出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2017.08.003
关键词
PBPK/PD; miRNA; BDNF; Neuroendocrine; System biology; PFOS
类别
资金
- European Union [603946]
- EuroMix (European Test and Risk Assessment Strategies for Mixtures) by the Horizon 2020 Framework Programme [633172]
- Universitat Rovira i Virgili under Marti-Franques Research Grants Programme
Integration of a dynamic signal transduction pathway into the tissue dosimetry model is a major advancement in the area of computational toxicology. This paper illustrates the ways to incorporate the use of existing system biological model in the field of toxicology via its coupling to the Physiological based Pharmacokinetics and Pharmacodynamics (PBPK/PD) model. This expansion framework of integrated PBPK/PD coupled mechanistic system pathway model can be called as system toxicology that describes the kinetics of both - the chemicals and - biomolecules, help us to understand the dynamic and steady-state behaviors of molecular pathways under perturbed condition. The objective of this article is to illustrate a system toxicology based approach by developing an integrated PBPK/PD coupled miRNA-BDNF pathway model and to demonstrate its application by taking a case study of the PFOS mediated neurotoxicity. System dynamic involves miRNA-mediated BDNF regulation, which plays an important role in the control of neuronal cell proliferation, differentiation, and survivability.
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