[Possible clinical application of SOD and free radical scavengers].

Ischemia-reperfusion injury in various organs has been discussed in connection with reactive oxygen species (ROS). Xanthine oxidase (XOD) has been believed to be the source of O2- to produce this injury of dogs and rats but XOD is not detected in hearts of men, pigs or rabbits. This suggests the importance of O2- produced by leukocyte NAD(P)H oxidase. We demonstrated in 1976 that 3 injections of Cu, Zn-SOD (superoxide dismutase) (i.v.) suppressed rat carrageenan paw edema. McCord succeeded with a single injection in the same model using polyethyleneglycol (PEG-SOD) of long retention time in the blood stream. Michelson's liposomal SOD had clinical effects on Behçet's disease, Crohn's disease etc. Stylenemaleimide (SMA)-SOD (Inoue) is now under experimental trial and recombinant human SOD (r-h-SOD) is today in phase II stage. The aim is to prevent myocyte damage or for kidney transplantation. So-called SOD mimics (Cu-complex etc), antioxidants (synthetic propyl gallate or natural flavonoids or tannins) and hydroxyl radical (.OH) scavengers such as DMTU (dimethylthiourea) are considered as a prototype for clinical application. Fe-chelators also attract attention, because Fe+2 produces the most reactive ROS, .OH radical.