Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Alp Sener

Abstract

Donation after cardiac death (DCD) grafts experience prolonged ischemia reperfusion injury (IRI) leading to higher rates of delayed graft function and failure. Recent studies have reported protective effects of hydrogen sulfide (H2S) against IRI. Our study aims at improving DCD renal graft outcomes by H2S supplementation in an in-vivo murine model of renal transplantation (RTx) and study the underlying mechanism in an in-vitro model using porcine kidney proximal-tubular-epithelial cells (LLC-PK1). H2S provided survival benefit, improved renal graft function and decreased renal injury in recipient rats. In our in-vitro model of LLC-PK1 cells, H2S demonstrated an important role mediated by mitochondria in the pathophysiological effects of IRI by reducing depolarization of the mitochondrial membrane and the amount of reactive oxygen species. In the long run, these findings would help bridge the gap between organ demand and supply by reducing the extent of renal IRI and delayed graft function in DCD donors.


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Urology Commons

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