Effects of di-(2-ethylhexyl) phthalate on the content and composition of hepatic mitochondrial and microsomal phospholipids in the rat

Feeding a 20% casein diet containing di-(2-ethylhexyl) phthalate (DEHP) at a 0.5% level to young male rats for 7 days resulted in a significant increase in hepatic phospholipids (PL), based either on per unit weight of the liver or on protein. Although the concentration of PL increased in both the mitochondrial and the microsomal fractions, the magnitude of the increase was much more marked in the former. The increase of PL in hepatic microsomal and mitochondrial fractions was attributed to increases in phosphatidylethanolamine (PE) and phosphatidylcholine (PC). In terms of percentage composition, PE increased significantly, whereas PC remained unchanged, leading to an elevation in the PE/PC ratio in both fractions. A similar response was observed in rats fed 0.1 to 0.5% DEHP for 30 days. Although hepatic PL accumulation was observed in rats fed a diet containing different dietary levels of casein and corn oil, the extent of the increase was much greater on a low protein diet. DEHP caused a decrease in the concentration of hepatic triglycerides (TG), and the magnitude of the reduction appeared to be greater in rats fed diets containing zero or low levels of essential fatty acids. The fatty acid profiles of PE and PC were modified differently by DEHP. Of interest was a significant increase in arachidonic acid in PE and a decrease in PC in two subcellular fractions examined. The rate of swelling of isolated mitochondria from the livers of rats fed DEHP was markedly slower than that of the controls. Some structural changes were also observed by electron microscopy.