ANTIOXIDANT PROPERTIES OF S-ADENOSYL-L-METHIONINE - A PROPOSED ADDITION TO ORGAN STORAGE FLUIDS

Glutathione (GSH) depletion adversely affects the survival of organ gr afts. Supplementation of commercial organ preservation solutions with GSH is complicated by the ease of oxidation of its thiol group and its ability to act as a pro-oxidant under certain conditions. Alternative sulphur-containing compounds such as S-adenosyl-L-methionine (SAM) ca n reduce ischaemia-reperfusion injury, possibly by acting as glutathio ne precursors, and are effective when added to preservation solutions. Although the antioxidant properties of GSH are known in some detail, there is little information on the ability of SAM to interact directly with reactive oxygen species (ROS) produced during ischaemia-reperfus ion injury. This work compares the interaction of SAM and GSH with sev eral ROS which may be formed during ischaemia-reperfusion. In a variet y of lipid peroxidation systems, SAM and GSH had little effect except at high concentrations (5 mM) where they became pro-oxidant. Scavengin g of O-2(.-) by both species was slow. SAM was less effective than GSH at preventing damage by peroxynitrite or HOCl. In contrast, SAM was m ore effective than GSH in scavenging hydroxyl radicals ((OH)-O-.) and in chelating iron ions to inhibit (OH)-O-. generation. Unlike GSH, SAM did not stimulate (OH)-O-. formation at low concentrations. The benef icial effects of SAM in preservation solutions could therefore include direct radical scavenging as well as acting as a precursor for intrac ellular GSH. (C) 1997 Elsevier Science Inc.