Research Project
2233590
DESCRIPTION: (adapted from applicant's abstract) The investigators have developed a class of synthetic, catalytic reactive-oxygen-species scavengers that mimic both superoxide dismutase and catalase. A prototype, EUK-8 is highly protective in a porcine model of adult respiratory distress syndrome. In this project, the potential therapeutic value of other compoundes in this model will be investigated. The specific aims are 1) to characterize enzymatic and key chemical properties of candidate compounds focusing on likely candidates for testing in the porcine model; 2) to evaluate candidate molecules in cell culture models that are relevant to adult respiratory distress syndrome, including those for neutrophil mediated endothelial damage; 3) to evaluate the selected candidate molecules in the porcine model, focusing on compounds with differing enzymatic activity ratios; and 4) using the porcine model, begin defining effective dosing parameters, focusing on a single molecule and clinically relevent dosing regimens.
