Altered transmembrane ionic flux in hepatocytes isolated from cirrhotic rats

Background/Aims: Although cirrhosis is known to be associated with many hep atocyte abnormalities, there is no well-established model to study the cell ular drug uptake process independent of hemodynamic effects. The purpose of the present study was to test the following hypothesis: hepatocytes isolat ed from cirrhotic animals may be used as a model to study the cellular abno rmalities associated with cirrhosis. Our hypothesis was tested by comparing the membrane potential (PD) of hepatocytes in anesthetized healthy and cir rhotic animals, and the PD and [H-3]palmitic acid clearance rate of hepatoc ytes isolated from healthy and cirrhotic animals. Methods: Mild to moderate cirrhosis was induced in female Sprague-Dawley ra ts by CCl4 administration. PD was recorded in anesthetized animals using in tracellular microelectrodes. Hepatocytes from those livers were subsequentl y isolated by collagenase perfusion for further determinations of PD and [H -3]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 (cirrh osis, n=13/group, p<0.01). The clearance rate of [H-3]palmitic acid was low er in hepatocytes isolated from cirrhotic animals (26%) than in those isola ted from healthy control animals (p<0.01). Conclusion: The results of this study indicate that hepatocytes isolated fr om cirrhotic animals may be used to study the cellular abnormalities associ ated with cirrhosis.