Intracellular and extracellular biomarkers of drug-induced liver injury


Hornby, R (2016) Intracellular and extracellular biomarkers of drug-induced liver injury. PhD thesis, University of Liverpool.

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Abstract

Drug-induced liver injury (DILI) is a common form of adverse drug reaction (ADR) seen within the clinic. Sensitive and specific circulating biomarkers would aid in the prediction of DILI early in its course. However, the current biomarkers of DILI, such as alanine transaminase (ALT) suffer from a lack of specificity and sensitivity. Because of this, we have examined both intracellular and extracellular biomarkers of DILI in order to validate and identify novel biomarkers of DILI. Protein tyrosine nitration (PTN), an intracellular marker of oxidative stress, has been shown to be present in paracetamol-DILI, and it is thought that the causative factor for its occurrence is mitochondrial damage. In order to test this, we used Furosemide (FS), a hepatotoxin not thought to cause mitochondrial injury or glutathione (GSH) depletion with the hypothesis that this compound would not generate PTN. First, we tested the role of GSH in protecting from PTN through depleting GSH in a mouse hepatoma cell line, followed by incubation with peroxynitrite. We found that GSH depletion was required in order to elicit PTN. Following this, we compared the ability of toxic doses of FS and paracetamol to cause PTN in mice. Interestingly, ... (continues)

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 08 Sep 2017 13:26
Last Modified: 03 Apr 2025 04:56
DOI: 10.17638/03001312
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3001312
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