novel approach for targeting oxidative stress in horses exhibiting recurrent airway obstruction

• Published in: Journal of animal physiology and animal nutrition 2009-04, Vol.93 (2), p.144-145
• Main Authors: Lepene, B.S, Buechner-Maxwell, V, Thatcher, C.D
• Format: Article
• Language: English
• ISSN: 0931-2439; 1439-0396
• DOI: 10.1111/j.1439-0396.2009.00921_7.x

Horses affected with Recurrent Airway Obstruction (RAO) exhibit inflammation and oxidative damage to lung cells. The main objective of this study was to develop a novel antioxidant delivery system (ADS) capable of targeting activated macrophages within the lower airways in order to reduce cellular oxidative damage. Specifically, this ADS consisted of folic acid and glutathione (GSH) linked to bisamine poly(ethylene oxide) (PEO). Folic acid conjugates exploit the over-expression of folate receptors on activated macrophages, allowing for the internalization of the ADS through receptor-mediated endocytosis. Initial results from in vitro studies demonstrated active targeting and uptake through folate receptor mediated endocytosis. GSH concentration in glutathione deficient RAW 264.7 cells (an immortalized murine macrophage cell line) was increased by more than 300% after incubation with the ADS for four hours effectively restoring 50% of the normal GSH concentration. F2-Isoprostanes, biomarkers for lipid oxidation, were reduced in RAW 264.7 cells by more than 67% after incubation with the ADS and exposure to zymosan, a free radical initiator. Evaluation of ADS as a treatment for equine RAO is underway and the results will be included in this presentation.