Impaired transport of lipopolysaccharide across the hepatocytes in rats with cerulein-induced experimental pancreatitis.
Hepatic dysfunction is one of the critical complications in acute pancreatitis but this mechanism is poorly understood. In patients with acute pancreatitis, hypoalbuminemia is often recognized, suggesting possible disturbance of hepatic transport of proteins and hepatic metabolites. The present study was undertaken to elucidate hepatic function in cerulein-induced pancreatitis from the viewpoint of intrahepatic vesicular transport. We examined the biliary excretion of lipopolysaccharide (LPS), whose pathway in the hepatocyte has been shown to be microtubule dependent. In vivo studies and ex vivo studies using isolated perfused rat liver (IPRL) showed that cumulative excretion of LPS in each period was significantly reduced, by 49 and 25%, respectively, compared with that in control rats. But studies of biliary secretion in vivo and ex vivo studies indicated statistical insignificance between the two groups. Moreover, biliary excretion of LPS was inhibited to 60% of the control by colchicine pretreatment, without affecting bile flow in IPRL, but gadolinium chloride had no effect. We conclude that transport of LPS across the hepatocyte from blood to bile is impaired in rats with cerulein-induced pancreatitis without being affected by Kupffer cell function. These results suggest that a disturbance of vesicular transport in hepatocyte may also occur in exocytosis and endocytosis via the sinusoidal membrane, cause impairment of hepatic transport of proteins and hepatic metabolites, and result in hepatic dysfunction in acute pancreatitis.
Hori
Y
Y
First Department of Surgery, Kobe University School of Medicine, Japan.
Takeyama
Y
Y
Ueda
T
T
Nishikawa
J
J
Yamamoto
M
M
Saitoh
Y
Y
D000818:Animals; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D002108:Ceruletide; D003078:Colchicine / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005682:Gadolinium / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D002108:Ceruletide; D005682:Gadolinium; D016650:Fluorescein-5-isothiocyanate; C038958:gadolinium chloride; D003078:Colchicine