Effect of ethanol on hepatic energy metabolism and intracellular pH in chronically ethanol-treated rats. A 31P NMR study of normoxic or hypoxic perfused liver.

31P Nuclear magnetic resonance spectroscopy has been used to investigate the combined effect of 70 mM ethanol administration and hypoxia on the energetic metabolism and cytosolic pH of the perfused liver isolated from naive, fasted or chronically ethanol-treated rats. Ethanol-treatment or fasting induce a similar 25% reduction in ATP levels, and a differential enhancement of Pi levels to 130% and 225% of control values, respectively. In the naive rats, acute ethanol administration triggers profound variations in high-energy phosphorylated metabolite levels with, in particular, a 300% increase in phosphomonoesters, mostly due to sn-glycerol-3-phosphate (G3P) accumulation. A 4 min hypoxic period in the presence of ethanol induced a further accumulation of G3P. In the livers from chronically ethanol-treated rats, the G3P level remains low during acute ethanol administration, despite the presence of glycogen, indicating an attenuation of the ethanol-induced redox shift. The combination of 70 mM ethanol and hypoxia leads to an increased G3P level in the livers of chronically ethanol-treated rats which is consistent with a sustained alcohol dehydrogenase activity. The subsequent cytosolic acidosis is significantly less pronounced in the chronically ethanol-treated rats than in naive rats. These observations illustrate the adaptation of metabolic processes occurring in the livers of chronically ethanol-treated rats, which results in an increased resistance to acute ethanol exposure and hypoxic stress.