PLASMA-KALLIKREIN CLEARANCE BY the LIVER of ACETAMINOPHEN-INTOXICATED RATS

PLASMA-KALLIKREIN CLEARANCE BY the LIVER of ACETAMINOPHEN-INTOXICATED RATS

Autor Detoledo, C. F. Google Scholar
Borges, D. R. Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo The liver synthesizes prokallikrein and is the main organ to clear the active enzyme (plasma-kallikrein) from circulation. This clearance, a receptor-mediated endocytosis, is calcium-independent and not affected by the blockade of Kupffer cells. the effects of endothelial cells blockade and of acetaminophen intoxication on the clearance of 10 nm rat plasma-kallikrein (RPK) by the isolated, exsanguinated and perfused rat liver are now reported. Endothelial cells blockade obtained by the addition of large excess (30 uM) of formaldehyde-treated serum albumin to the perfusion fluid does not affect the hepatic clearance of RPK (the half-lives of hepatic uptake were 15.5 +/- 1.0 min in the absence versus 16.5 +/- 1.4 min in the presence of the treated protein, p > 0.05). Some livers were perfused 24 hours after acetaminophen intoxication: 6.6 mmol/kg given i.p. after a 42-hour period of fast. Hepatocyte injury suggested by elevated aminotransferase activity (ALT 10 times control value, AST 30 times control value), acute phase inflammatory response (serum alpha2-macroglobulin increase) and reduced synthetic function (serum albumin decrease), was confirmed histologically and only zone 3 hepatocytes were necrotic. A 66-hour period of fast does not affect by itself the hepatic clearance of RPK (16.9 +/- 1.3 min of half-life of hepatic uptake) when compared with the control group (15.5 +/- 1.0 min, p > 0.05). On the other hand the RPK clearance by the livers of rats previously intoxicated with acetaminophen was markedly deficient (the half-life of hepatic uptake was 39.2 +/- 3.2 min). These findings suggest that RPK is internalized by hepatocytes, preferentially by those of the perivenular zone of the hepatic acinus.
Idioma Inglês
Data de publicação 1993-01-01
Publicado em Life Sciences. Oxford: Pergamon-Elsevier B.V., v. 52, n. 17, p. 1451-1459, 1993.
ISSN 0024-3205 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 1451-1459
Fonte http://dx.doi.org/10.1016/0024-3205(93)90069-F
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:A1993KT80900007
Endereço permanente http://repositorio.unifesp.br/handle/11600/25296

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