DRUG-INDUCED PROTEOLYSIS - CORRELATION WITH EDEMA-REDUCING ABILITY

  • 1 January 1976
    • journal article
    • research article
    • Vol. 57  (3) , 266-273
Abstract
A very strong correlation exists between acid and neutral protease activity levels in the skin, the acid protease activity level of the edema fluid, and the edema-reducing ability of the benzopyrones and related drugs in studies on rats. Macrophages, which are believed to be the main cells affected by the drugs, are very common in thermally injured tissues. Their lysosomal enzymes work at an acid pH. Since the main acid protease is cathepsin D, the overall acid protease levels are representative of changes in cathepsin D levels. Elevated levels are concomitant with more complete and rapid digestion of accumulated protein. The resulting fragments then can rapidly leave the injured tissues, freeing the edema fluid. This form of proteolysis is very much different from that which is used by pharmacologists as a measure of inflammation. Normal proteolysis in inflammation represents an estimate of tissue derangement, but the proteolysis induced by drugs such as the benzopyrones represents a means of lessening some of the more injurious effects of this derangement. This is confirmed.