Selenomethionine enhances transplant organ preservation by attenuating oxidative stress-induced proteolysis in rats.

Abstract

Selenomethionine (SeMet) increases glutathione peroxidase (GPx) activity, a seleno-enzyme with an antioxidant function that counteracts reactive oxygen species (ROS). After ablation, transplant organs generate ROS during irrigation-reperfusion injury. GPx1 can be downregulated during hypoxia in ablated organs. ROS can oxidize proteins, inducing proteolysis, which compromises the transplant outcome. SeMet administration to living donors can decrease proteolysis in transplant organs, improving their preservation. Accordingly, SeMet was administered to rats for 7 days. After this period, the liver, heart, and kidneys were ablated, and proteins extracted at different postmortem intervals (PMI). Total protein analysis showed a lower protein concentration decrease in kidneys and heart from SeMet-supplemented rats after a 6 hs PMI. Molecular weight changes of proteins to proteolysis products (PPs) were studied by size exclusion chromatography (SEC). SeMet decreased PPs (<29.5 kDa) in the liver, kidneys, and heart. Specific analysis of GPx1 proteolysis by affinity chromatography coupled to inductively coupled plasma mass spectrometry (AF-ICP-MS) showed that SeMet administration decreased GPx1 proteolysis 24% in the liver and 16.8% in the heart. SeMet administration reduced the proteolysis velocity of GPx1 (V_GPx1) in heart. SeMet administration to living donors for seven days decreased proteolysis in transplant organs, improving its conservation.