A novel in vivo31P-nuclear magnetic resonance technique for assessment of liver failure induced by chlorinated-hydrocarbon in mice

Abstract

Novel in vivo 31P-, 1H- and 2H-nuclear magnetic resonance (NMR) techniques for accurate and noninvasive assessment of hepatic failure induced by chlorinated-hydrocarbons, major environmental toxicants found in tap water, were developed. Male mice were administered halocarbons (trichloromethane, tetrachloromethane, tetrachloroethane; 0.0001-1,000 μg/kg of body weight once or daily for 4 weeks; p.o.). In vivo NMR spectra acquired noninvasively and quantitatively were used to evaluate their hepatic energy metabolism and blood flow rate, and liver failure was estimated by conventional blood biochemical and histopathological methods. At doses of 0.1-1,000 μg/kg, a significant decrease in liver ATP level was seen 0.5 h after administration and continued to drop showing maximum reduction between 1-2 h and recovered by 120 h. However, no changes in serum transaminase activities or liver histopathology were seen at doses of 1 or 10 μg/kg. In mice with repeated administration (0.0001-1 μg/kg), no liver failure was detected by conventional biochemical or histopathological methods, but consistent decreases in the hepatic ATP level and liver blood flow rate were detected by the NMR techniques. In conclusion, in vivo NMR techniques are highly sensitive (at least 100-fold more sensitive than conventional methods) and are useful for toxicological assessment of environmental pollutants in tap water.