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Title: Pharmacological preconditioning of human hepatocytes
Author: McNally, Stephen Justin
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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Liver surgery, be it for resection or transplantation, causes injury to the organ. Pre-treatment of the liver to protect it from injury would be of clinical interest as poor liver function following surgery can be life threatening. Such “preconditioning” treatments could be applied to both elective liver surgery and liver transplantation. The aim of this project was to establish the ability of certain pharmacological agents to induce the stress response in human hepatocyte, and to protect them from the type of injury seen in surgical practice.  Curcumin, an extract of the spice turmeric, was found to induce the enzyme heme oxygenase-1. It preconditioned hepatocytes to survive in models mimicking both ischaemia-reperfusion injury and the cold preservation injury which occurs during transplantation. Cyclosporin A was also studied as a putative preconditioning agent. However, although it did have some effect on the stress response, it did not precondition human hepatocytes. As an extension of the work on heme oxygenase-1, the effect of a promoter polymorphism in the human HO-1 gene was studied. This work has demonstrated that curcumin does pharmacologically precondition human hepatocytes in vitro. It has also strengthened the evidence for heme oxygenase-1 as a target for preconditioning strategies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available