In vivo and in vitro 31P magnetic resonance spectroscopic studies of the hepatic response of healthy rats and rats with acute hepatic damage to fructose loading.
The hepatic response to a fructose challenge for control rats, and rats subjected to an acute sublethal dose of carbon tetrachloride (CCl4) or bromobenzene (BB), was compared using dynamic in vivo 31P MRS. Fructose loading conditions were used in which control rats showed only a modest increase in hepatic phosphomonoester (PME), and a small decrease in ATP, Pi, and intracellular pH after fructose administration. Both CCl4 and BB-treated rats showed a much greater fructose-induced accumulation of PME than did controls. Trolox C, a free radical scavenger, prevented most of this PME increase. BB-treated rats, given sufficient time to recover from the hepatotoxic insult, responded to the fructose load similarly to controls. Liver aldolase activities of control, toxicant-treated rats, and toxicant plus Trolox C-treated rats correlated inversely with PME accumulation after fructose loading (correlation coefficient: -0.834, P < 0.05). Perchloric acid extracts of rat livers studied by in vitro 31P MRS confirmed that the PME accumulation after fructose loading is mainly due to an increase in fructose 1-phosphate. These studies are consistent with the aldolase-catalyzed cleavage of fructose 1-phosphate being rate-limiting in hepatic fructose metabolism, and that the CCl4 and BB treatment modify and inactivate the aldolase enzyme.
Lu
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Department of Chemistry and Biochemistry, University of Guelph, Ontario, Canada.
Locke
S J
SJ
Brauer
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001969:Bromobenzenes / Q000009:adverse effects*; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D002839:Chromans / Q000494:pharmacology; D005632:Fructose / Q000378:metabolism*; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D005636:Fructosephosphates / Q000378:metabolism; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D005994:Glycerophosphates / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010755:Organophosphates / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D010758:Phosphorus / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology
D000975:Antioxidants; D001969:Bromobenzenes; D002839:Chromans; D005636:Fructosephosphates; D005958:Glucosephosphates; D005994:Glycerophosphates; D010755:Organophosphates; D010767:Phosphorylcholine; D014810:Vitamin E; C032284:fructose-1-phosphate; D010758:Phosphorus; D005632:Fructose; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; C029620:alpha-glycerophosphoric acid; D002251:Carbon Tetrachloride; C032036:bromobenzene; D005634:Fructose-Bisphosphate Aldolase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D010634:Phenobarbital