Copper and aspirin treatment increase the antioxidant activity of plasma

Copper (Cu) complexes of a number of compounds have increased anti-inflammatory efficacy over the native compound. In the present study, Cu and acetylsalicylic acid (ASA) were administered to rabbits over a one week period. At the end of this time, ocular inflammation was induced by intravitreal injection of endotoxin. ASA caused a slight reduction in the inflammatory response at 24 hours, but this response was not further decreased when Cu was added to the treatment regimen. However, there was a gradual and significant increase in antioxidant activity in the plasma of animals in the combined treatment group which could not be accounted for by a Cu-ASA complex, an increase in the concentration of known plasma protein antioxidants (ceruloplasmin and transferrin) or an increase in superoxide dismutase activity. The compound(s) responsible for this increased activity has a molecular weight greater than 10,000 Da. A large increase in plasma antioxidant activity may have a protective effect in other models of inflammation and provide a mechanism for the proven increase in anti-inflammatory efficacy of Cu-chelates of many compounds.