PLASMA KALLIKREIN CLEARANCE BY THE LIVER OF CHRONIC CARBON TETRACHLORIDE-TREATED RATS

We have previously reported that the endocytosis of rat plasma kallikrein (RPK) by hepatocytes is a calcium-independent and beta-galactoside-dependent mechanism. We now report the clearance of RPK by the liver of four groups of rats: normal, inflamed (48 h ex-turpentine) and two groups chronically treated with CCl4 (52 mg/kg per week, intragastrically, for 9-12 weeks). Each liver was isolated, exsanguinated and perfused at 37 degrees C with 30 mL of BSA-Krebs-Henseleit-bicarbonate medium containing 10 nmol/L RPK. Although all rats received the same mild CCl4 treatment, the liver histology showed that they evolved either to severe hepatitis (serum alanine aminotransferase [ALT] 4852 +/- 885 U/L, parenchymatous necrosis in the perivenous region) or to compensated cirrhosis (serum ALT 209 +/- 42 U/L, vigorous fibrous encircling regeneration nodules); neither jaundice nor ascites was noted. The results show that serum albumin was not altered among the groups and that: the acute-phase response by itself (inflamed group) increased RPK clearance rate (3.01 +/- 0.59 mL/min) as compared with the normal group (1.85 +/- 0.14 mL/min); the CCl4 treatment, although induced an acute-phase response, decreased (P < 0.01) RPK clearance rates (0.80 +/- 0.11 mL/min hepatitis group and 0.98 +/- 0.10 mL/min cirrhosis group). These findings suggest that the hepatic clearance rate of plasma kallikrein is an early indicator of liver injury.