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Journal of Lipid Research, Vol. 4, 68-74, January 1963
Copyright © 1963 by Lipid Research, Inc.

Studies on fatty liver induction by 4-aminopyrazolopyrimidine

J. Frank Henderson

Department of Pharmacology, The George Washington University, School of Medicine, Washington, D. C.

The effects of the adenine analogue, 4-aminopyrazolopyrimidine, on lipid metabolism in mouse liver have been studied in an attempt to ascertain the mechanism by which this drug causes fatty livers. Injection of 1 mg of APP caused an increase in the total liver lipid of 3-to 4-fold in 24 hr, which was almost entirely accounted for as neutral lipid. There was a small increase in the cholesterol content of treated livers, but no change in the amount of phospholipid. Treatment with APP inhibited the incorporation of acetate-C¹⁴ into lipids of liver slices in vitro, but had little effect on the oxidation of acetate-C¹⁴ and palmitate-C¹⁴ in vitro. The plasma lipid concentration was decreased by APP treatment, and this was caused by a drop in triglycerides and cholesterol, whereas phospholipids and FFA did not change. Palmitate-C¹⁴ was taken up less well by livers of mice treated with APP than by livers of control mice. Although APP caused a profound inhibition of incorporation of orotic acid-C¹⁴ into RNA, the incorporation of glycine-C¹⁴ into liver and plasma proteins was not diminished. The hyperlipemia normally elicited by Triton WR-1339 was inhibited by APP, which strongly suggests that this compound inhibits the secretion of triglycerides from the liver.

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				J. Andersen and J. Dietschy Cholesterogenesis: derepression in extrahepatic tissues with 4-aminopyrazolo (3,4-d) pyrimidine Science, September 3, 1976; 193(4256): 903 - 905. [Abstract] [PDF]