EFFECT OF CHRONIC ETHANOL-CONSUMPTION ON THE ENERGY-STATE AND STRUCTURAL STABILITY OF PERIPORTAL AND PERIVENOUS HEPATOCYTES

This study was implemented to evaluate whether perivenous cells experience functional alterations due to a deficit in oxygen tension resulting from ethanol oxidation in the periportal regions of the lobule. Periportal and perivenous hepatocytes were prepared from ethanol-fed and control animals (Lieber-DeCarli diet, 31 days). These cells were either incubated at various oxygen tensions by varying the composition of the gases utilized to equilibrate the incubation buffers (0, 5, 25, and 95% oxygen) or they were unincubated. They were analyzed for adenine nucleotide and inorganic phosphate concentrations and from these data phosphorylation potentials and energy charge values were determined. Under highly aerobic conditions no differences were observed in the energy states of the cells irrespective of their source (control vs ethanol-fed; periportal vs perivenous). The ATP concentrations, phosphorylation potentials, and energy charge values indicated that the energy states of cells from both ethanol-fed and control rats were maintained at relatively high levels in incubations with 5 and 25% oxygen. However, unincubated cells and those incubated at 0% oxygen demonstrated lowered energy states and the decreases were most striking in hepatocytes from ethanol-fed animals. Measurements of LDH loss and trypan blue exclusion indicate that cell leakage and viability loss occur when cells are incubated under anoxic and hypoxic conditions. At low oxygen tensions perivenous cells from ethanol-fed rats demonstrated much greater loss of structural stability than did the other cell preparations. These observations indicate that decreased energy state is one factor which contributes to cell damage in hepatocytes from ethanol-fed animals. Moreover, perivenous cells from ethanol-fed animals seem to be particularly vulnerable to damage under hypoxic conditions. (C) 1995 Academic Press, Inc.