The relevance of microRNAs and circadian rhythms in drug safety


Starkey Lewis, Philip (2012) The relevance of microRNAs and circadian rhythms in drug safety. Doctor of Philosophy thesis, University of Liverpool.

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Abstract

Drug-induced liver injury (DILI) is a serious adverse drug reaction (ADR) that is frequently encountered during drug development, representing a major cause of drug attrition. Furthermore, DILI is also a serious concern in the clinic, accounting for approximately half of all acute liver failure cases. Paracetamol overdose (acetaminophen; APAP) accounts for the majority of DILI-associated cases of ALF encountered in patients. The identification and development of novel biomarkers of DILI that are sensitive, specific, and rise early during hepatotoxicity are urgently required in the clinic and in the laboratory. Two liver-specific microRNAs (miRNAs) have recently been described that serve as sensitive and early markers of APAP-induced acute liver injury (APAP-induced ALI) in a mouse model. Together with the superior liver-enrichment of some liver-enriched miRNAs, these potential markers need to be assessed in patients for the clinical promise. Moreover, further work is warranted to test these potential markers in alternative pre-clinical models with other compounds to gain a better understanding regarding sensitivity of release, mechanism of release and circulatory kinetics. Furthermore, in separate work discussed ... (continues)

Item Type: Thesis (Doctor of Philosophy)
Additional Information: Date: 2012-09 (completed)
Uncontrolled Keywords: Biomarkers, microRNA, Liver, Paracetamol, Acetaminophen, Furosemide, Clinical Circadian Rhythms
Subjects: ?? RM ??
Divisions: Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 03 Sep 2013 11:31
Last Modified: 03 Apr 2025 04:56
DOI: 10.17638/00011753
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/11753
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