| Abstract: | Terephthalic acid at 20 mg/kg/day in lowered serum cholesterol and triglyceride levels in rats. The cholesterol content was lowered in the lipoprotein fractions. The effects of the agents on de novo lipid synthesis showed that similar enzymes were affected in rat liver and small intestinal mucosa cells as when compared to in vitro tissue culture cells from rats and humans, e.g. reduction of acyl CoA cholesterol acyl transferase and elevation of neutral cholesterol ester hydrolase activities suggest that net cholesterol esters deposition in foam cells should be reduced and plaque growth should be slowed. The suppression of LDL receptor binding and degradation by the drug suggest that less apoB lipoproteins are taken up by peripheral tissues. The elevated HDL receptor binding and internalization in the liver suggest that the drug accelerates cholesterol return to the liver. Additional studies show that cholesterol and bile acid secretion in the bile is elevated. However, the bile acids secreted are not lithogenic. Acute toxicity studies show that the agent appears to be safe in rodents. Two observations of increased serum alkaline phosphophatase levels and increased liver vacuolation suggest some alteration of hepatic cell morphology, which requires further investigation. |
