The effect of orally administered secondary autoxidation products of linoleic acid on the activity of detoxifying enzymes in the rat liver.

Radioactive secondary autoxidation products of linoleic acid were administered orally to rats and the incorporation of radioactive substances into lipids was investigated in the liver. The radioactive substances were significantly incorporated into hepatic mitochondrial and microsomal lipids 12 h after the administration. 80% of the radioactivity in mitochondria was detected in neutral lipids. The radioactivity in microsomal neutral lipids significantly decreased and the activity in phospholipids increased 12 h after the administration. On the other hand, contents of lipid peroxide and thiobarbituric acid reactive substances in liver were significantly increased by 40% at 15 h after the administration of the secondary autoxidation products. Activity of marker enzymes used for an indication of the hepatic injury was also elevated. Glutathione peroxidase activity increased 3-fold and catalase activity increased 1.5-fold. Activity of mitochondrial NAD-dependent aldehyde dehydrogenase, however, was decreased by 50%. It seems likely that the secondary autoxidation products orally administered are detoxified in the hepatic mitochondria, metabolized to neutral lipids, and further metabolized to phospholipids in microsomes, while as the incorporated secondary autoxidation products induces hepatic injury by lipid peroxidation.