Hepatic clearance of tissue-type plasminogen activator and plasma kallikrein in experimental liver fibrosis.

Abstract

We have previously shown that tissue-type plasminogen activator (tPA) and rat plasma kallikrein (RPK) share a common, but not unique, pathway for liver clearance. To evaluate the hepatic clearance of both proteases in experimental liver fibrosis. The hepatic clearance of these proteases was studied in porcine serum-induced liver fibrosis using the isolated and perfused rat liver model. To better interpret the results, we also studied four other experimental groups: the turpentine oil-induced acute-phase response (AP group), AP group followed by GdCl3 administration (AP/Gd group), CCl4-induced cirrhosis (CCl4 group) and normal group. The tPA clearance decreased significantly by both fibrotic and cirrhotic rat livers whereas the RPK clearance was not altered by the fibrotic rat liver. The hepatic clearance of tPA was reduced in the AP and AP/Gd groups; on the other hand, RPK clearance was increased in the AP group and, interestingly, this effect was neutralized by concomitant GdCl3 administration. We observed that tPA and RPK clearances were affected differently by fibrosis as well as by different stimuli of the acute-phase response, despite the fact that they share a common hepatic clearance mechanism in normal livers, and they were equally affected in cirrhosis.