Hepatic D-galactosamine toxicity studied with localized in vivo 31P magnetic resonance spectroscopy in intact rats.
Spatially resolved 31P magnetic resonance spectroscopy (MRS) at 4.7 T was applied to noninvasively assess liver phosphorus metabolites in a biochemically well-characterized model of hepatotoxicity induced by injection of a sublethal dose of D-galactosamine (galN). A newly developed hybrid method based on spectral localization with B0 and B1 gradients was employed to obtain multivoxel spectra in intact anesthesized rats. Spatially localized in vivo spectra were recorded 0 to 26 h after galN injection of female rats. In response to galN exposure, diphosphodiester peaks ascribed to UDP-hexosamines became detectable by 4 h and persisted up to 26 h. A metabolite coresonating with inorganic phosphate increased rapidly in intensity by 2 h after galN and returned to baseline by 18 h; this resonance was shown not to be Pi and was assigned to galN-1-phosphate by subsequent high resolution MRS experiments on extracts prepared from these livers. These results confirmed in vivo the metabolic perturbations described previously for this model of hepatotoxicity following biochemical studies based on classical extraction methods. Unlike the in vitro studies, however, these noninvasive experiments provided additional information on the time course of metabolic alterations on the same animal.
Weisdorf
S
S
Center for Magnetic Resonance Research, Department of Pediatrics, University of Minnesota Medical School, Minneapolis 55455.
Hendrich
K
K
Buchthal
S
S
Wike
J
J
Bratt
G
G
Merkle
H
H
Garwood
M
M
Uğurbil
K
K
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D005260:Female; D005688:Galactosamine / Q000378:metabolism* / Q000506:poisoning; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods*; D010725:Phosphocreatine / Q000032:analysis / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000032:analysis / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010725:Phosphocreatine; D010758:Phosphorus; D005688:Galactosamine; D000255:Adenosine Triphosphate; D010744:Phosphoric Monoester Hydrolases; D010727:Phosphoric Diester Hydrolases