P-31 and H-1 NMR spectroscopic studies of liver extracts of carbon tetrachloride-treated rats

NMR spectroscopy was used to examine hepatic metabolism in cirrhosis with a particular focus on markers of functional cellular hypoxia. P-31 and H-1 N MR spectra were obtained from liver extracts from control rats and from rat s with carbon tetrachloride-induced cirrhosis. A decrease of 34% in total p hosphorus content was observed in cirrhotic rats, parallelling a reduction of 40% in hepatocyte mass as determined by morphometric analysis. Hypoxia a ppeared to be present in cirrhotic rats, as evidenced by increased inorgani c phosphate levels, decreased ATP levels, decreased ATP:ADP ratios (1.72 +/ - 0.40 vs 2.48 +/- 0.50, p < 0.01), and increased inorganic phosphate:ATP r atios (2.77 +/- 0.48 vs 1.62 +/- 0.24, p < 0.00001). When expressed as a pe rcentage of the total phosphorus content, higher levels of phosphoethanolam ine and lower levels of NAD and glycerophosphoethanolamine were detected in cirrhotic rats. Cirrhotic rats also had increased phosphomonoester:phospho diester ratios (5.73 +/- 2.88 vs 2.53 +/- 0.52, p < 0.01), These findings a re indicative of extensive changes in cellular metabolism in the cirrhotic liver, with many findings attributable to the presence of intracellular hyp oxia. Copyright (C) 1999 John Wiley & Sons, Ltd.