PEG superoxide dismutase derivatives: anti-inflammatory activity in carrageenan pelurisy in rats

Two derivatives of superoxide dismutase (SOD) with monomethoxypolyethyleneglycol, having different molecular weights (46,000 and 121,000 D) and different plasma half-lives are tested in carrageenan pleurisy in rats after single i.v. injection. The compounds were prepared following an original method where the polymer is activated by trichlorophenylchloroformate to give a phenylcarbonate which is reactive towards the protein amino groups. The anti-inflammatory activity of derivatives results correlated to their kinetics, lasting longer for the derivative with the longest half-life (SOD-PEG 18). SOD activity, in plasma of rats treated with SOD-PEG 18, is still present 24 hour after carrageenan, in agreement with the prolonged anti-inflammatory activity. Moreover SOD-PEG 18 diffuses well in pleural exudate, as it is evidentiated from the increase with time of exudate/plasma concentration ratio.