Human MnSOD Research Articles

Anti-inflammatory activity of superoxide dismutases: inhibition of adriamycin induced edema in rats.

Various superoxide dismutases from different sources, containing Cu, Mn or Fe at the active centre, have been examined with respect to anti-inflammatory activity in a model using adriamycin-induced edema in rats. Very large differences in efficiency are observed, the most active being E. coli Mn-SOD and bovine Cu-SOD. The Fe-SOD from E. coli is active whereas P. leiognathi Fe-SOD is not. Human Mn-SOD shows no significant activity and homologous rat Cu-SOD is totally inactive. Yeast Cu-SOD shows pro-inflammatory properties. Anti-inflammatory activity is not a function of molecular weight or circulation life-time.

Pharmacokinetic and anti-inflammatory properties in the rat of superoxide dismutases (Cu SODs and Mn SOD) from various species

The comparison of the anti-inflammatory properties (carrageenan paw edema in the rat) of exogenous Cu SODs from various species and human Mn SOD administered at doses corresponding to clinical schedules, shows that human and bovine Cu SOD are fully active, whereas rat Cu SOD and Mn SOD are inefficient. This difference does not correspond to the similarity of pharmacokinetic properties (blood levels, subcellar location in kidney cortex) of the Cu proteins or to the increased circulating life time of Mn SOD. The pharmacological activity of exogenous SOD is limited to heterologous Cu SODs in the rat. A similar problem may occur in man. The true mechanism of action Cu SOD remains to be elucidated.