The effects of chronic ethanol consumption on the intact rat liver studied by in vivo 31P NMR spectroscopy.
In vivo 31P nuclear magnetic resonance (NMR) spectroscopy provides unique opportunities to study the biochemistry of an organ within the intact animal in a totally non-invasive way. We have used in vivo and in vitro 31P NMR spectroscopy to study steady state changes in the major phosphorus-containing metabolites of the rat liver in control and chronically ethanol-treated rats. Chronic (4 month) ethanol treatment caused a statistically significant increase in the inorganic phosphate and phosphodiester resonances of rat liver in in vivo 31P NMR spectra relative to pair-fed control rats. Phosphomonoester and adenosine 5'-triphosphate resonances, as well as intracellular pH, were not appreciably altered. The effects of chronic ethanol treatment were particularly apparent in the response of the liver to a metabolic challenge of glycerol. Glycerol is phosphorylated almost exclusively in the liver and metabolized predominately via glycolysis and gluconeogenesis. Our in vivo 31P NMR results after administration of glycerol showed a significant increase in the phosphomonoester resonance in the liver of chronic ethanol-treated rats but not for their pair-fed controls. In vitro 31P NMR studies of perchloric acid extracts of liver showed that the increase was due to an accumulation of sn-glycerol 3-phosphate. This effect is due to the NAD(+)-dependent glycerol 3-phosphate dehydrogenase step being inhibited in the chronic ethanol-treated rats. This glycerol test may be useful in assessing the ability of the liver to rapidly regenerate NAD+ in situ and may be a more sensitive indicator of redox imbalance than steady state ratios of redox pairs (e.g., lactate/pyruvate).
Guelph-Waterloo Center for Graduate Work in Chemistry, University of Guelph, Ontario, Canada.
M
M
Brauer
M F
MF
Ling
D000255:Adenosine Triphosphate / Q000032:analysis; D000437:Alcoholism / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D005994:Glycerophosphates / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010710:Phosphates / Q000032:analysis; D010725:Phosphocreatine / Q000032:analysis; D010758:Phosphorus / Q000032:analysis; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains
D005994:Glycerophosphates; D010710:Phosphates; D010725:Phosphocreatine; D010758:Phosphorus; D000431:Ethanol; D000255:Adenosine Triphosphate; C029620:alpha-glycerophosphoric acid; D005990:Glycerol