Proton magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) have been used to study the response of the rat liver in situ to
bromobenzene, a classic hepatotoxicant. A localized region of high
proton signal intensity was seen in the perihilar region of the liver 24 hr after injection of a sublethal dose of
bromobenzene. The signal intensity of the entire liver was increased at 48 hr with a gradual return approaching control values by 120 hr. These results are consistent with acute hepatic
edema followed by repair of the damaged tissue. In vivo 31P MRS studies of the same rat livers were performed under conditions whereby localized, quantitative spectra could be obtained without surgical intervention. Initial concentrations of the major endogenous
phosphorus-containing metabolites within the livers of control rats were 2.97 +/- 0.43 mM for the phosphomonoesters (PME), 2.92 +/- 0.56 mM for
inorganic phosphate, 11.3 +/- 1.0 mM for phosphodiesters (PDE), 4.09 +/- 0.54 mM for
ATP, and 0.56 +/- 0.50 mM for
ADP and the intracellular pH was 7.39 +/- 0.14 (mean +/- SD, n = 10).
Bromobenzene was found to cause statistically significant (p less than 0.05) changes in several of these metabolites: a decrease in hepatic
ATP levels (20% at 24 hr; 27% at 48 hr), a decrease in PDE levels (15% at 24 hr; 18% at 48 hr), and an increase in the PME (63% at 24 hr; 84% at 48 hr). Both the
proton MRI and the 31P MRS changes have an onset of 15-20 hr and maximum effect at 25-60 hr, but the MRS changes returned to normal well before the MRI changes. The decreased
ATP levels indicate deleterious effects of
bromobenzene on the bioenergetic status of the liver in situ, while the increase in PME, due to a selective increase in
phosphocholine, suggests the activation of a
phosphatidylcholine-specific phospholipase C in response to tissue damage.
Trolox C, a potent inhibitor of lipid peroxidation, prevented the
bromobenzene-induced hepatic
edema (i.e., the increase in
proton MRI signal intensity) and the bioenergetic deterioration (i.e., the decrease in
ATP levels). However, the
bromobenzene-induced increase in PME levels was not prevented by
Trolox C. These results indicate that the process of lipid peroxidation plays a significant role in the hepatotoxicity of
bromobenzene within the intact animal.