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

The effects of alpha-tocopherol on the hydrazine-induced changes in th e structure of mitochondria and those in the enzymatic and nonenzymati c antioxidant systems of the liver were investigated using rats as exp erimental animals. Animals were divided into four groups: animals of t he first group were placed on a powdered diet containing 1.0% hydrazin e 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 fourt h day and thereafter for up to 7 days, the control diet was replaced b y 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-tocopher ol partly prevented the hydrazine-induced formation of megamitochondri a in the liver. (2) Treatment of animals with hydrazine induced remark able increases in the contents of alpha-tocopherol in mitochondria (4. 8 times), microsome (1.4 times), and homogenate (2.9 times) of the liv er compared with those of the control. Treatment of animals with alpha -tocopherol did not raise the concentration of alpha-tocopherol in mit ochondria of the liver. The highest concentration of alpha-tocopherol in motochondria of the liver was obtained in animals given hydrazine p lus alpha-tocopherol (7.2 times higher than the control). (3) The amou nt of lipid-soluble fluorophores as an indicator of nonenzymatic oxida tive stress was remarkably increased in mitochondria, microsome, and h omogenate of the liver of hydrazine-treated animals. (4) Among enzymes protecting the cell from the oxidative stress activities of superoxid e dismutase and glutathione peroxidase were almost the same among four groups of animals, while the activity of catalase was decreased disti nctly 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 fr ee radicals, prevents the hydrazine-induced formation of megamitochond ria in the liver. However, we failed to correlate free radicals to bio chemical and physicochemical changes of mitochondrial membranes induce d by hydrazine. Previously, we have demonstrated that a ratio of unsat urated to saturated fatty acids in phospholipid domains of mitochondri al membranes increases with hydrazine treatment. Since increases in th e 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.