Bile flow and biliary sulfobromophthalein sodium excretion in rats with liver cirrhosis and portacaval shunt.
In order to study the combined effect of end-to-side portacaval shunt and chronic liver damage on biliary organic anion transport, the rat model of thioacetamide-induced chronic liver injury was utilized. Compared with sham-operated animals, bile flow and maximal biliary excretion (Tm) of sulfobromophthalein sodium (BSP) was decreased in rats 9 weeks after shunt operation. If rats with shunts were treated for 8 weeks with thioacetamide, an agent causing hepatic fibrosis and pseudolobule formation, BSP transport from the hepatocyte into bile was further diminished. Compared with the shunted controls, the thioacetamide-treated rats with shunts had elevated serum bilirubin and alkaline phosphatase concentrations, and on electron microscopy their livers had dilated bile canaliculi with a decreased number of microvilli. Non-shunted rats treated with thioacetamide for 8 weeks had similar but less severe changes in the canalicular ultrastructure. Bile flow and BSP Tm were not influenced by thioacetamide treatment alone, perhaps due to the marked liver hypertrophy in these animals. These results indicate that canalicular active transport of organic anions is more sensitive to the effect of thioacetamide in animals with portacaval shunts than in those with sham operations. A similar impairment of hepatic organic anion handling by hepatotoxic compounds might be the consequence of portasystemic shunts in patients with liver cirrhosis.
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001663:Bilirubin / Q000097:blood; D001693:Biological Transport, Active; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology* / Q000601:surgery; D008111:Liver Function Tests; D008297:Male; D008854:Microscopy, Electron; D011167:Portacaval Shunt, Surgical; D051381:Rats; D013448:Sulfobromophthalein; D013853:Thioacetamide
D013853:Thioacetamide; D013448:Sulfobromophthalein; D000469:Alkaline Phosphatase; D001663:Bilirubin