EFFECT OF ETHANOL ON ADENOSINE-TRIPHOSPHATE, CYTOSOLIC-FREE CALCIUM, AND CELL INJURY IN RAT HEPATOCYTES - TIME-COURSE AND EFFECT OF NUTRITIONAL-STATUS

The events implicated in the early phases of acute ethanol-induced hep atocyte injury and their relation with the nutritional status of the l iver are not clearly defined. We aimed to determine the effect of etha nol on ATP and cytosolic free Ca2+ in hepatocytes isolated from fed or fasted rats. Cell injury was assessed by LDH release and trypan blue uptake, ATP by [P-31]NMR spectroscopy, and cytosolic free Ca2+ with ae quorin. In control conditions, cells from fasted animals had a lower A TP level (-52%) and a higher cytosolic free Ca2+ (+101%) than did thos e isolated from fed animals. Ethanol caused a dose-dependent cell inju ry in both groups. At all ethanol doses, greater damage occurred when using hepatocytes isolated from fasted rats. In both groups, a dose-de pendent decrease in ATP content and a rise in cytosolic free Ca2+ were seen. The magnitude of these changes were significantly greater in th e fasted group. In conclusion, these data showed that fasting affects the energy status and cytosolic free calcium level in hepatocytes; eth anol causes a dose-dependent cell injury that occurs in association wi th a fall in ATP and a rise in cytosolic free Ca2+ levels. The nutriti onal status of an animals is an important determinant of the severity of ethanol-induced damage to liver cells.