SUPPRESSION OF THE HYDRAZINE-INDUCED FORMATION OF MEGAMITOCHONDRIA IN THE RAT-LIVER BY ALPHA-TOCOPHEROL

The effects of alpha-tocopherol on the hydrazine-induced changes in the structure of mitochondria and those in the enzymatic and nonenzymatic antioxidant systems of the liver were investigated using rats as experimental animals. Animals were divided into four groups: animals of the first group were placed on a powdered diet containing 1.0% hydrazine for 7 days; those of the second and third groups received a control diet and alpha-tocopherol (ip, daily, 700 mg/kg body wt). On the fourth day and thereafter for up to 7 days, the control diet was replaced by a 1.0% hydrazine diet for the animals of the second group; those of the fourth group served as the control. After 10 days (in the case of animals of the first group, 7 days), animals were sacrificed. Results obtained were as follows: (1) Treatment of animals with alpha-tocopherol partly prevented the hydrazine-induced formation of megamitochondria in the liver. (2) Treatment of animals with hydrazine induced remarkable increases in the contents of alpha-tocopherol in mitochondria (4.8 times), microsome (1.4 times), and homogenate (2.9 times) of the liver compared with those of the control. Treatment of animals with alpha-tocopherol did not raise the concentration of alpha-tocopherol in mitochondria of the liver. The highest concentration of alpha-tocopherol in motochondria of the liver was obtained in animals given hydrazine plus alpha-tocopherol (7.2 times higher than the control). (3) The amount of lipid-soluble fluorophores as an indicator of nonenzymatic oxidative stress was remarkably increased in mitochondria, microsome, and homogenate of the liver of hydrazine-treated animals. (4) Among enzymes protecting the cell from the oxidative stress activities of superoxide dismutase and glutathione peroxidase were almost the same among four groups of animals, while the activity of catalase was decreased distinctly in hydrazine-treated animals. Administration of alpha-tocopherol to these animals did not improve its activity. The present study has clearly demonstrated that alpha-tocopherol, a typical scavenger for free radicals, prevents the hydrazine-induced formation of megamitochondria in the liver. However, we failed to correlate free radicals to biochemical and physicochemical changes of mitochondrial membranes induced by hydrazine. Previously, we have demonstrated that a ratio of unsaturated to saturated fatty acids in phospholipid domains of mitochondrial membranes increases with hydrazine treatment. Since increases in the ratio specified above are a key event in the membrane fusion process we are now studying how the ratio is modified by hydrazine focussing on desaturase activity in the liver, and results will be reported soon. (C) 1994 Academic Press, Inc.