Proton magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy studies of bromobenzene-induced liver damage in the rat.
Respiratory-gated proton magnetic resonance imaging was used to study the response of the rat liver in situ to bromobenzene, a classic hepatotoxicant. A localized region of high proton signal intensity in the perihilar region of the liver was seen 24-48 hr after an intraperitoneal injection of bromobenzene. Localized proton magnetic resonance spectra from within this region indicated that the increased proton signal intensity was not due to accumulation of fat in the liver, but primarily due to a longer T2 for the proton resonance of water. This is consistent with acute edema in this localized region. In vivo 31P magnetic resonance spectroscopy studies of the same rat livers in situ were performed. Spectroscopic conditions were determined whereby localized, quantitative 31P spectra could be obtained. Using these methods, 10 mmol/kg bromobenzene was found after 24 hr to cause a number of statistically significant (p less than 0.05) effects: a decrease in adenosine 5'-triphosphate levels from 4.1 +/- 0.5 to 3.0 +/- 0.5 mM, a decrease in phosphodiester levels from 11.3 +/- 0.9 to 9.3 +/- 0.7 mM and an increase in the phosphomonoesters from 3.0 +/- 0.4 to 5.5 +/- 1.2 mM (mean +/- standard deviation). High resolution in vitro 31P spectra of perchloric acid extracts of these rat livers showed that the increased phosphomonoester resonance was due to a selective 4.3-fold increase in phosphocholine. Thus, our in vivo and in vitro 31P magnetic resonance spectra are consistent with the hypothesis that a phosphatidylcholine-specific phospholipase C (generating phosphocholine and diacylglycerol) is activated during tissue damage. Both the imaging and spectroscopy results obtained with bromobenzene closely resemble CCl4-induced liver changes previously reported, and may reflect a generalized response of the liver to any acutely acting toxic chemical.
Brauer
M
M
Guelph-Waterloo Center for Graduate Work in Chemistry, University of Guelph, Ontario, Canada.
Locke
S
S
D000818:Animals; D001969:Bromobenzenes / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001969:Bromobenzenes; C032036:bromobenzene