N. Manabe et al., A novel in vivo P-31-nuclear magnetic resonance technique for assessment of liver failure induced by chlorinated-hydrocarbon in mice, BIOMED RES, 21(6), 2000, pp. 317-326
Novel in vivo P-31-, H-1- and H-2-nuclear magnetic resonance (NMR) techniqu
es for accurate and noninvasive assessment of hepatic failure induced by ch
lorinated-hydrocarbons, major environmental toxicants found in tap water, w
ere developed. Male mice were administered halocarbons (trichloromethane, t
etrachloromethane, tetrachloroethane; 0.0001-1,000 mug/kg of body weight on
ce or daily for 4 weeks; p.o.). In vivo NMR spectra acquired noninvasively
and quantitatively were used to evaluate their hepatic energy metabolism an
d blood flow rate, and liver failure was estimated by conventional blood bi
ochemical and histopathological methods. At doses of 0.1-1,000 mug/kg, a si
gnificant decrease in liver ATP level was seen 0.5 h after administration a
nd continued to drop showing maximum reduction between 1-2 h and recovered
by 120 h. However, no changes in serum transaminase activities or liver his
topathology were seen at doses of 1 or 10 mug/kg. In mice with repeated adm
inistration (0.0001-1 mug/kg), no liver failure was detected by conventiona
l biochemical or histopathological methods, but consistent decreases in the
hepatic ATP level and liver blood flow rate were detected by the NMR techn
iques. In conclusion, in vivo NMR techniques are highly sensitive (at least
100-fold more sensitive than conventional methods) and are useful for toxi
cological assessment of environmental pollutants in tap water.