Diethylaminoethoxyhexestrol causes hypertriglyceridemia in guinea pigs.
Treatment of rats, monkeys and man with diethylaminoethoxyhexestrol causes phospholipid storage in liver and other tissues. However, this drug has not been reported to alter plasma lipoprotein levels. When guinea pigs were treated with diethylaminoethoxyhexestrol, the fasting plasma triacylglycerol levels increased dramatically, from 43 to 1281 mg/dl, after only five doses of 12.5 mg/kg. Diethylaminoethoxyhexestrol-treated guinea pigs had reduced postheparin lipase activity. In addition, in vitro assays showed that this agent inhibited guinea pig postheparin lipoprotein lipase. It is hypothesized that diethylaminoethoxyhexestrol causes hypertriglyceridemia in guinea pigs because these animals are known to have low levels of serum activator for lipoprotein lipase and may be unusually susceptible to agents that inhibit lipoprotein lipase activity. The ability to produce hypertriglyceridemia in guinea pigs provides an animal model in which the metabolic consequences of hypertriglyceridemia can be studied.
Hostetler
K Y
KY
Pappu
A S
AS
Witztum
J L
JL
D000818:Animals; D002784:Cholesterol / Q000097:blood*; D006168:Guinea Pigs; D006589:Hexestrol / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D014280:Triglycerides / Q000097:blood*
D014280:Triglycerides; D006589:Hexestrol; D002784:Cholesterol; D010740:Phospholipases; D010741:Phospholipases A; D008071:Lipoprotein Lipase; C100116:hexestrol bis(diethylaminoethyl ether)