Therapeutic effects of tetrathiomolybdate on hepatic dysfunction occurring naturally in Long-Evans Cinnamon (LEC) rats: a bona fide animal model for Wilson's disease.

Long-Evans Cinnamon (LEC) rats were fed a diet containing 7 ppm Cu and 30 ppm Cu from 60 days after birth. Fischer (Fischer group) and LEC (LEC-control group) rats fed a 7 ppm Cu diet showed normal growth throughout the whole period (60 to 125 days after birth). On the other hand, LEC rats fed the 30 ppm Cu diet had decreased body weight and showed slight jaundice at around 100 days after birth. Tetrathiomolybdate (TTM, 10 mg/kg bw) was injected sub-cutaneously at 101 and 105 days after birth into half of the LEC rats fed the 30 ppm Cu diet. LEC rats given TTM (LEC+TTM group) recovered their body weight and the jaundice rapidly disappeared. However, LEC rats without TTM (LEC-TTM group) had sharply decreased body weight and showed severe jaundice at 103 days after birth. The hepatic Cu concentration in LEC+TTM rats (460 micrograms/g) exceeded that of LEC-control rats (330 micrograms/g) at 125 days after birth. Our data suggest that TTM is effective for treatment of acute hepatic injury in the LEC rat.