Supplementation With Hydrogen Sulfide Helps Mitigate The Effects Of Ischemia Reperfusion Injury In A Model Of Donation After Cardiac Death Renal Transplantation

Author

Jaskirandeep Kaur Grewal, The University of Western OntarioFollow

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.

Recommended Citation

Grewal, Jaskirandeep Kaur, "Supplementation With Hydrogen Sulfide Helps Mitigate The Effects Of Ischemia Reperfusion Injury In A Model Of Donation After Cardiac Death Renal Transplantation" (2015). Electronic Thesis and Dissertation Repository. 3053.
https://ir.lib.uwo.ca/etd/3053