IN-VIVO AND IN-VITRO P-31 MAGNETIC-RESONANCE SPECTROSCOPIC STUDIES OFTHE HEPATIC RESPONSE OF HEALTHY RATS AND RATS WITH ACUTE HEPATIC DAMAGE TO FRUCTOSE LOADING

The hepatic response to a fructose challenge for control rats, and rat s subjected to an acute sublethal dose of carbon tetrachloride (CCl4) or bromobenzene (BB), was compared using dynamic in vivo P-31 MRS. Fru ctose loading conditions were used in which control rats showed only a modest increase in hepatic phosphomonoester (PME), and a small decrea se in ATP, P-1, and intracellular pH after fructose administration. Bo th CCl4, and BB-treated rats showed a much greater fructose-induced ac cumulation of PME than did controls. Trolox C, a free radical scavenge r, prevented most of this PME increase. BB-treated rats, given suffici ent time to recover from the hepatotoxic insult, responded to the fruc tose load similarly to controls. Liver aldolase activities of control, toxicant-treated rats, and toxicant plus Trolox C-treated rats correl ated inversely with PME accumulation after fructose loading (correlati on coefficient: -0.834, P < 0.05). Perchloric acid extracts of rat liv ers studied by in vitro P-31 MRS confirmed that the PME accumulation a fter fructose loading is mainly due to an increase in fructose I-phosp hate. These studies are consistent with the aldolase-catalyzed cleavag e of fructose 1-phosphate being rate-limiting in hepatic fructose meta bolism, and that the CCl4 and BB treatment modify and inactivate the a ldolase enzyme.