Date: Tuesday, May 5, 2015
Session Name: Poster Session D: Innate Immunity in Transplantation
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Introduction: Ischemia reperfusion injury (IRI) in organ transplant often manifests itself as delayed graft function (DGF). DGF is associated with increased morbidity and deleterious effects on short and long term graft survival. Hydrogen sulphide (H2S), has been shown to have significant protective effects on IRI. Several H2S donor molecules are in existence but many have significant systemic effects, thus potentially precluding them from clinic use. Given that most of the protective mechanisms behind H2S concentrate on mitochondrial protection, our objective was to determine if the newly derived mitochondrial targeting H2S donor molecule (AP39) would be more efficacious in protecting renal cells against IRI compared to the commonly used agent GYY4137.
Methods: Porcine kidney tubular epithelial cells (LCC-PK1) were exposed to warm ischemia (glucose and nutrient deficient media, 37°C, in a hypoxia chamber at 1% O2 saturation) for 24 hours, without any treatment (Group 1,control), with various doses of AP39 (Group 2) or various doses of GYY4137 (Group 3) followed by 24hr of reperfusion (21% O2 in a glucose and nutrient rich media at 37°C). Cells were subsequently assessed for cell viability, apoptosis, necrosis, reactive oxygen species (ROS) production and the expression of mitochondrial protective pro-apoptotic and anti-apoptotic markers.
Results: AP39 increased cell viability and almost rescued hypoxic cells to normoxic viability (P<0.01) compared to group1 and 3. AP39 significantly minimized cell apoptosis (p<0.05). AP39 also inhibited the up-regulation of Bid (p<0.05) and down-regulation of Bcl-2 (p<0.05).
Conclusion: This is the first description showing the benefit of mitochondrial targeted H2S donor molecules in warm IRI. AP39 appears to have more potent protective effect against tissue hypoxia compared to GYY4137, by reducing ROS and anti-apoptotic proteins.
To cite this abstract in AMA style:Aboalsamh G, Saha M, Lobb I, Grewal J, Luke P, Wood M, Whiteman M, Sener A. Mitochondrial Hydrogen Sulphide Donor Molecules Are More Effective Against Hypoxic Injury in Renal Tubular Epithelial Cells [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/mitochondrial-hydrogen-sulphide-donor-molecules-are-more-effective-against-hypoxic-injury-in-renal-tubular-epithelial-cells/. Accessed April 22, 2021.
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