31P and 1H 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. (31)P and (1)H NMR spectra were obtained from liver extracts from control rats and from rats with carbon tetrachloride-induced cirrhosis. A decrease of 34% in total phosphorus content was observed in cirrhotic rats, parallelling a reduction of 40% in hepatocyte mass as determined by morphometric analysis. Hypoxia appeared to be present in cirrhotic rats, as evidenced by increased inorganic 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 ratios (2.77 +/- 0.48 vs 1.62 +/- 0.24, p < 0.00001). When expressed as a percentage of the total phosphorus content, higher levels of phosphoethanolamine and lower levels of NAD and glycerophosphoethanolamine were detected in cirrhotic rats. Cirrhotic rats also had increased phosphomonoester:phosphodiester ratios (5.73 +/- 2.88 vs 2.53 +/- 0.52, p < 0.01). These findings are indicative of extensive changes in cellular metabolism in the cirrhotic liver, with many findings attributable to the presence of intracellular hypoxia.
Harvey
P J
PJ
Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, ACT 0200, Australia. Peta.Harvey@anu.edu.au
Gready
J E
JE
Hickey
H M
HM
Le Couteur
D G
DG
McLean
A J
AJ
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D019906:Nuclear Magnetic Resonance, Biomolecular; D010758:Phosphorus; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D014020:Tissue Extracts / Q000032:analysis
D011522:Protons; D014020:Tissue Extracts; D010758:Phosphorus; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002251:Carbon Tetrachloride