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Functional role of haem oxygenase-1 (HO-1) induction prior to hypothermic storage and reperfusion in renal tissue

Balogun, Elizabeth Olayinka; (2003) Functional role of haem oxygenase-1 (HO-1) induction prior to hypothermic storage and reperfusion in renal tissue. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

In renal transplantation, delayed graft function and primary nonfunction are major sources of graft loss and morbidity. Since the shortage of donor organs is a major problem, it is imperative to develop methods capable of preserving organs after significant periods of warm and cold ischaemia, and at the same time minimise the reperfusion injury associated with transplantation. One approach is based on the stimulation of a specific inducible stress protein known as haem oxygenase-1 (HO-l), which may act by producing antioxidant, anti-inflammatory and cytoprotective molecules. The aims of the present study were: l) to establish methods for upregulation, identification and measurement of HO-l in experimental models; 2) to investigate the role of HO-1 and its products, CO and bilirubin, in protecting renal tissues during hypothermic storage and subsequent reperfusion. 3) to search for novel "pharmacological preconditioning agents" that are capable of selectively activating the HO-1 gene in renal tissues. The effect of HO-1 induction on renal function by various inducers was investigated after hypothermic storage and reperfusion in a) an ex vivo system of isolated perfused kidney; b) an autograft transplant model; and c) in vitro cell culture. The results show that, following induction of HO-1 in renal tissue, the enzymatic activity was maintained during hypothermia, and some beneficial effects on renal function could be observed after storage and reperfusion. In cell cultures, novel inducers of HO-1 were identified which may prove useful in the future for the development of more effective preservation solutions. In Chapter 1, a general introduction is given; methods are described in Chapter 2; experiments on the induction of HO-1 in renal tissue are reported in Chapter 3; in Chapters 4-6 results from studies on whole kidney perfusion in vitro and auto-transplantation in vivo are presented; in Chapters 7 and 8, studies on novel inducers of HO-1 using renal cells in culture are reported; in Chapter 9 a general discussion is given.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Functional role of haem oxygenase-1 (HO-1) induction prior to hypothermic storage and reperfusion in renal tissue
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Haem oxygenase
URI: https://discovery.ucl.ac.uk/id/eprint/10107318
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