Increased mortality in septic rats after leupeptin application.

Loss of body weight induced by catabolic stress situation like trauma, burns, operation, sepsis is caused by both enhanced proteolysis and diminished synthesis (1,2). This catabolic phase is characterized by the net breakdown of body protein, primarily in skeletal muscle. Odessey reported elevated rates of protein degradation in the soleus muscle from a burned limb, while no effects on the rates of protein synthesis were detected (3). The mechanism responsible for increased muscle breakdown is not understood. It has been reported that the rate of proteolysis in muscle is coupled with the activity of cathepsin B and D and also other proteinases (4,5). Most of the work done in elucidating the role of lysosomal proteinases in mediating protein degradation has been done in cell culture and perfused organ preparation. In this study we investigated the effect of Leupeptin, a thiol proteinase inhibitor on septic rats.