Effect of Benzyl N-Benzyl Carbethoxyhydroxamate on Cholesterol Metabolism in the Rat. ∗

Abstract

Summary

In 3 experiments, male Wistar rats (185 g) were fed 2% benzyl N-benzyl carbethoxyhydroxamate (W-398) for 3 weeks. The rats exhibited marked weight loss (losing 40 g while the controls were gaining 50-80 g); livers of the drug-fed group were larger (5.4-7.0% body wt) compared with the controls (39-4.4% body wt) and liver cholesterol levels were significantly elevated (avg of 3 experiments: drug—858 mg/100 g and control—279 mg/100 g). The compound had no effect upon serum cholesterol levels. In one experiment, in which W-398 was fed as 0.5% of the diet, the rats gained 30% less weight than did the normals, their livers were larger and their liver cholesterol levels were significantly higher than were those of the control rats. The data suggest a continuing synthesis of cholesterol in rats fed W-398 but an apparent inability to transfer it from the liver.

When either acetate- 1-¹⁴C or mevalonate-2-¹⁴C was injected into the drug-treated rats they converted more (but not significantly more) of the substrate to cholesterol than did the controls. Liver slices from W-398-treated rats converted less acetate-1-14C to cholesterol than did liver slices from control rats.