The effects of 3,5,5-trimethylcyclohexanol on hepatic cholesterol synthesis, bile flow and biliary lipid secretion in the rat.
The chemical trimethylcyclohexanol (TMC) is closely related to menthol, the major component of a terpene preparation with known choleretic and cholelitholytic activity. Its effects on hepatic cholesterol synthesis and bile secretion were examined in the rat. In both acute and long-term dosing experiments TMC significantly inhibited hepatic S-3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase. TMC was a potent choleretic, with detectable effects on bile flow at low doses, which also reduced coupling of cholesterol secretion to bile salt secretion. Single large doses tended to lower biliary cholesterol output and caused significant reduction in cholesterol saturation index after biliary diversion for 1 h. TMC and its widely prescribed ester cyclandelate, which is rapidly degraded to TMC after ingestion, should be investigated further as potential cholelitholytic treatments in man.
D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight; D002784:Cholesterol / Q000096:biosynthesis*; D003511:Cyclohexanols / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D003511:Cyclohexanols; D010743:Phospholipids; C037269:3,3,5-trimethylcyclohexanol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases