THE CERIUM-INDUCED LIVER-INJURY AND OXIDATIVE DRUG-METABOLISM IN DBA/2 AND C57BL/6 MICE

The influence of the known hepatotoxic agent, cerium (Ce) on the activity of liver microsomal monoxygenases, especially coumarin 7-hydroxylase (COH) was investigated in two inbred strains of male mice, DBA/2N and C57BL/6N. Ce was injected intravenously in three doses (0.5, 1.0 and 2.0 mg/kg body wt) and the animals were killed 24 or 72 h later. On the basis of histological assessment of the liver, C57BL/6N mice are apparently more resistant to the hepatotoxic effect of Ce. At 24 h, COH activity was increased in a dose-dependent manner in DBA/2 animals, whereas no change was seen in C57BL/6N animals. A significant increase in all other enzymes studied, cytochrome P-450 (P450), ethoxycoumarin 0-deethylase and ethoxyresorufin 0-deethylase, was seen in DBA/2 mice injected with the highest dose of Ce. At 72 h Ce increased CON activity, as well as other enzymes, in C57BL/6N mice in a dose-dependent manner, whereas in DBA/2 mice the increase was only seen after the two lower doses, the highest dose causing severe morphological changes in the liver structure and a clear decrease in COH and other activities. The distribution studies with Ce-141 showed that C57BL/6N livers contained more Ce than DBA/2 livers after the highest dose.