Altered transmembrane ionic flux in hepatocytes isolated from cirrhotic rats

Background/Aims: Although cirrhosis is known to be associated with many hepatocyte abnormalities, there is no well-established model to study the cellular drug uptake process independent of hemodynamic effects. The purpose of the present study was to test the following hypothesis: hepatocytes isolated from cirrhotic animals may be used as a model to study the cellular abnormalities associated with cirrhosis. Our hypothesis was tested by comparing the membrane potential (PD) of hepatocytes in anesthetized healthyand cirrhotic animals, and the PD and [3H]palmitic acid clearance rate of hepatocytes isolated from healthy and cirrhotic animals. Methods: Mild to moderate cirrhosis was induced in female Sprague-Dawley rats by CCl4 administration. PD was recorded in anesthetized animals using intracellular microelectrodes. Hepatocytes from those livers were subsequently isolated by collagenase perfusion for further determinations of PD and [3H]palmitic acid uptake. Results: The mean (±SEM) hepatocyte PD from intact rat livers was 38±1 mV (control) and −32±1 mV (cirrhosis; n=6/group, p<0.01). The PD (mean±SEM) in isolated hepatocytes was −21±1 mV (control) and −15±1 mV (cirrhosis, n=13/group, p<0.01). The clearance rate of [3H]palmitic acid was lower in hepatocytes isolated from cirrhotic animals (26%) than in those isolated from healthy control animals (p Conclusion: The results of this study indicate that hepatocytes isolated from cirrhotic animals may be used to study the cellular abnormalities associated with cirrhosis.