Repression of fibrinolysis in scalded rats by administration of Serratia protease.

The oral administration Serratia protease (SP), an antiinflammatory oral drug, to scalded rats markedly repressed the activation of fibrinolysis induced by the scalding. The repression was most effective when SP was given 3 hr prior to scalding, and a statistically significant repression was observed at a dose of 5 mg/kg. The repressive effect of SP was dependent on its proteolytic activity and was far stronger than those of other proteases tested. The repression was observed also by the intravenous injection of SP at a dose as low as 0.2 microgram/kg, which corresponded to a blood concentration of about 4 ng/ml. In this case, too, the proteolytic activity was essential. In rat blood, SP existed as a complex with a plasma protease inhibitor, alpha 1-macroglobulin (alpha 1 M), with a molar binding ratio of 1:1, still retaining about 20% of its original caseinolytic activity. This ratio, together with the alpha 1 M concentration in rat plasma and the molecular weights of SP and alpha 1 M, enabled the estimation that at the effective SP concentration (4 ng/ml) only 1 out of 20,000 parts of alpha 1 M molecules in plasma took part in the complex formation.