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To differentiate between the "intact" and "sick" cell hypothesis explaining decreased clearance of endo- and xenobiotics, we measured uptake of taurocholate and ouabain in hepatocytes isolated from cirrhotic rat liver. Cirrhosis was induced by chronic exposure of male Sprague-Dawley rats to phenobarbital and carbon tetrachloride. Uptake of [14C]taurocholate and [3H]ouabain was measured by a rapid filtration technique. Hepatocytes from cirrhotic liver were as viable as control hepatocytes--as judged by trypan blue exclusion and lactate dehydrogenase release--but consumed 28% less oxygen. Vmax of both taurocholate (3.16 +/- 0.95 vs. 0.40 +/- 0.35 nmoles X min-1 X 10(6) cells-1; p less than 0.001) and ouabain (2.16 +/- 0.78 vs. 0.83 +/- 0.26 nmoles X min-1 X 10(6) cells-1; p less than 0.005) was significantly reduced. These results are compatible with the "sick" cell hypothesis.
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