Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on lipid profiles in tissue of the Fischer rat

Abstract

Female Fischer 344 rats were given single oral doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 10, 50 or 100 microgram/kg, and sacrificed 1, 3, 10, 14 or 21 days later. The fatty livers caused by a sub-lethal dose of TCDD involved a temporary increase in triglyceride and free fatty acid levels, with a persistent decrease in levels of sterol esters. In contrast, the fatty livers resulting from a lethal dose of TCDD involved a large increase in cholesterol esters and free fatty acids, with little change in triglyceride levels. These changes appeared to result in part from damage sustained by lysosomes. TCDD also altered the lipoprotein composition of the serum, the fatty acid composition of various lipid classes in liver and serum, and the ultrastructure of the liver (formation of myeloid bodies). A rapid, dose-dependent effect of TCDD, was the elevation of levels of organic-soluble fluorescent pigment in the heart. This pigment was found to match a previously characterized fraction of lipofuscins in fluorescence spectrum and chromatographic properties. The relatioship of these observations to a possible mechanism of toxicity for TCDD involving radical-induced lipid peroxidation is discussed.