INHIBITION OF HYDROXYL RADICAL PRODUCTION BY LACTOBIONATE, ADENINE, AND TEMPOL

Superoxide and hydroxyl free radicals are strongly implicated in the d eleterious effects of reperfusion of grafted organs. Iron ions are cri tical in the Fenton-like reaction that generates oxygen-free radicals from H2O2. Using the ADP/Fe2+/H2O2 (OH)-O-.-generating system, we demo nstrated that components of an organ-preservation solution (Henri Mond or solution): sodium lactobionate, adenine, and a nitroxide radical: 4 -hydroxy-2,2,6,6-tetramethylpiperidine-n-oxyl (TEMPOL), showed unexpec ted inhibition properties on the production of hydroxyl radicals by co mplexation of Fe2+ for lactobionate and nitroxide or Fe3+ for adenine. This inhibition was 75.5% at 12 mM lactobionate. Moreover, a complete inhibition was observed at 50 mM. At 0.25 mM adenine, the reduction w as 14.8% (maximum effect: 34.1%). Henri Mondor solution, at an identic al adenine and lactobionate concentration, inhibited the radical produ ction by 91.5%, indicating an additive effect. Nitroxide totally inhib ited (OH)-O-. production by the ADP/Fe2+/H2O2 system (maximum effect: 95.6%) and partially the production by an O-2(.-) generating system (m aximum effect: 74.8%). Thus, the association of these three components in preservation solutions would be an original method to limit the re perfusion injury observed in isolated ischemic organs.