Cf. Toledo et al., PLASMA KALLIKREIN CLEARANCE BY THE LIVER OF CHRONIC CARBON TETRACHLORIDE-TREATED RATS, Journal of gastroenterology and hepatology, 10(2), 1995, pp. 165-168
We have previously reported that the endocytosis of rat plasma kallikr
ein (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, intragastrica
lly, for 9-12 weeks). Each liver was isolated, exsanguinated and perfu
sed at 37 degrees C with 30 mL of BSA-Krebs-Henseleit-bicarbonate medi
um 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 compensate
d cirrhosis (serum ALT 209 +/- 42 U/L, vigorous fibrous encircling reg
eneration nodules); neither jaundice nor ascites was noted. The result
s show that serum albumin was not altered among the groups and that: t
he acute-phase response by itself (inflamed group) increased RPK clear
ance 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-pha
se response, decreased (P < 0.01) RPK clearance rates (0.80 +/- 0.11 m
L/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.