The effects of hypoxia on the bioenergetics of liver in situ in chronic ethanol-treated rats: a noninvasive in vivo 31P magnetic resonance spectroscopy study.

Abstract

The effects of hypoxia on bioenergetic parameters of the livers of rats with and without chronic ethanol (CE) treatment has been studied in a totally noninvasive manner, using in vivo 31P magnetic resonance spectroscopy (MRS). The effects of hypoxia (10% oxygen for 55 minutes) on the levels of ATP, inorganic phosphate (Pi), phosphomonoesters (PME) and phosphodiesters (PDE) were followed with time. The CE and control rats (four pairs) were starved for 16-20 hours to eliminate the effects of any ethanol still present within the liver. To complement the in vivo studies, perchloric acid extracts from rats (four pairs for each stage) at the three stages, initial (normoxic), hypoxic and recovery, were analyzed using in vitro high resolution 31P MRS. After hypoxic challenge, the hepatic Pi and PME levels increased much more significantly and more quickly for the CE rats compared to those of controls, and ATP levels decreased more dramatically for CE rats. The recoveries of Pi and PME levels after return to normoxic conditions were incomplete for the CE rats in contrast to the controls. The hepatic extract analyses showed that several different PMEs increased during hypoxia, including alpha-glycerophosphate, phosphocholine, AMP, IMP and glycolytic metabolites, and that total hepatic Pi increased during hypoxia in addition to cytoplasmic Pi. CE-treated rat livers in situ are bioenergetically more sensitive to a hypoxic challenge than are control rat livers, even in the absence of endogenous ethanol. This is consistent with a model of CE-induced liver damage in which CE-treated livers already have centrolobular hypoxia under normoxic conditions and cannot adequately compensate for additional hypoxic stress.