Prospects for treatment of free radical-mediated tissue injury.

Toxic metabolites of oxygen are generated normally by aerobic metabolism in cells and this generation can significantly increase in certain pathologic conditions. When endogenous antioxidant defense capabilities are exceeded by this oxidant flux, tissue injury occurs. This process can be intercepted pharmacologically at different levels with agents that scavenge reactive oxygen metabolites, block their generation, or enhance endogenous antioxidant capabilities. In many situations, such as the treatment of post-ischaemic reperfusion injury, efficacy of antioxidant is related primarily to the proportionate magnitude of the total injury sustained that is due to an antioxidant mechanism. This approach has shown great promise in animal models of clinical problems and has been tested successfully in early, controlled clinical trials.