Collagenase inhibition in colonic mucosa by proteinase inhibitors

The effect of proteinase inhibitors on collagenase activity in rabbit colonic mucosa, both in vitro and in vivo, has been measured by a tissue culture method. Aprotinin, when applied to colonic explants at doses of 20 and 40 KIU, significantly reduced the lytic activity by 97.3% and 99.1% respectively (P less than 0.001). At doses of 100, 200 and 400 KIUs, lysis was completely abolished. Rectal biopsies taken from rabbits at 4, 24, 48 and 72 h following either intramuscular, oral or rectal administration of soy or lima bean trypsin inhibitor showed significant reductions in collagenolytic activity (P less than 0.001). The effects were greater and more rapid by the enteral routes of administration and the lima bean trypsin inhibitor was more effective than that of soy bean. The results suggest an inhibitory effect on collagenase by local lumenal action on colonic mucosa. Proteinase inhibitors may thus have a role to play in colorectal surgery by reducing collagen breakdown and increasing the strength of the healing anastomosis.