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.
Toledo
C F
CF
Gastroenterology Division, Escola Paulista de Medicina, São Paulo, Brazil.
Kouyoumdjian
M
M
Lanzoni
V P
VP
Borges
D R
DR
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D007610:Kallikreins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar
D007610:Kallikreins