Drug induced proteolysis: a correlation with oedema reducing ability

A very strong correlation was shown to exist between acid and neutral protease activity levels in the rat skin, the acid protease activity level of the edema fluid, and the edema reducing ability of the benzo pyrones and related drugs. 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 benzo pyrones represents a means of lessening some of the more injurious effects of this derangement. The results presented here strongly confirm this.