Role of hepatic copper-metallothionein on liver function of Long-Evans cinnamon rats with a new mutation causing hereditary hepatitis.

Liver slices from Wistar and Long-Evans Cinnamon (LEC) rats were incubated while open to the atmosphere to assess the liver function in LEC rats. Leakages of glutamic-oxaloacetic transaminase (GOT) and lactic dehydrogenase (LDH) into the medium were significantly lower in the LEC rat than in the Wistar rat. Furthermore, no pronounced enhancement of the concentration of thiobarbituric acid-reactive substances (TBARS) was found in the LEC rat. Hepatic Cu and Cu-metallothionein (Cu-MT) concentrations were 355.0 +/- 18.7 micrograms/g liver and 2559 +/- 181 micrograms/g protein in the LEC rats, whereas Wistar rats showed 4.1 +/- 0.1 Cu microgram/g liver accompanied by 16 +/- 4 micrograms/g protein of MT. The decrease of intrahepatic Cu-MT in LEC rats was stimulated by incubation with Fenitrilotriacetate (Fe-NTA). There was a direct correlation between the enhancement of TBARS and disappearance of Cu-MT. Our results suggest that hepatic Cu-MT in LEC rats protects against liver injury stimulated by oxidative stress.