Induction of metallothionein synthesis by menadione or carbon tetrachloride is independent of free radical production

Abstract

The relationship between induction of hepatic metallothionein (MT) synthesis and lipid peroxidation by free radical production following an injection of menadione or carbon tetrachloride (CCl 4) in mice was studied. The hepatic concentration of MT was increased by menadione significantly at 25 mg/kg or higher. A significant increase in thiobarbituric acid (TBA) value, indicative of lipid peroxidation, was observed in the liver at menadione doses of 62.5 mg/kg or higher. Both the MT and the TBA value in the liver were significantly increased at the low dose of CCl 4. The concentration of MT was increased significantly 4–8 hr after administrations of these compounds. The increase of TBA value over time was similar to that of MT concentration after administration of CCl 4, but not after administration of menadione. The MT concentration in the menadione group was higher than that in the CCl 4 group, and the TBA level in the menadione group was lower than that in the CCl 4 group. Pretreatment with vitamin E caused a significant reduction in the TBA value, but did not affect the MT level in the liver. The concentration of MT did not significantly correlate with the TBA value in either the menadione or the CCl 4 group. Pretreatment with phenobarbital, which promotes free radical production, did not influence induction of MT synthesis following an injection of menadione or CCl 4. Neither l-buthionine sulfoximine nor 2-cyclohexen-1-one, which decreases hepatic glutathione, influenced the induction of MT by menadione. These data suggest that induction of MT synthesis by menadione or CCl 4 is independent of free radical production in the liver.