The hepatic adaptive response to repeat acetaminophen exposure


Eakins, RM (2016) The hepatic adaptive response to repeat acetaminophen exposure. PhD thesis, University of Liverpool.

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Abstract

The adaptive response to chemical stress arises when an injurious exposure to a drug initiates phenotypic changes in the liver. These phenotypic changes limit hepatotoxicity upon subsequent exposures, and constitute an important evolutionary safeguard to the individual's survival. The factors governing hepatic adaptation to the popular analgesic and antipyretic acetaminophen (paracetamol) represent valuable research avenues, since acetaminophen toxicity is a leading cause of emergency hospital admissions through accidental and intentional overdose. Knowledge of the broader mechanisms governing hepatic adaptation to chemical exposure are limited; and concerning acetaminophen specifically, the research focus to date has been on select proteins implicated in metabolism. The aim of this thesis was to investigate the molecular mechanisms of adaptation to chemical stress in two preclinical models using the classical hepatotoxin acetaminophen. These models have been characterised through clinically accepted toxicological and histopathological assessments, establishing acetaminophen-induced injury in high dose acetaminophen exposure groups in both rat and mouse models. A global proteomic analysis of rat liver has ... (continues)

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences > Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 16 Aug 2016 09:21
Last Modified: 03 Apr 2025 04:56
DOI: 10.17638/03001381
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3001381
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