dc.contributor.author | Berkhout, Theo | |
dc.contributor.author | Simon, Helen M. | |
dc.contributor.author | Jackson, Brian | |
dc.contributor.author | Yates, John | |
dc.contributor.author | Pearce, Nigel | |
dc.contributor.author | Groot, Pieter H E | |
dc.contributor.author | Bentzen, Craig | |
dc.contributor.author | Niesor, Eric | |
dc.contributor.author | Kerns, William D. | |
dc.contributor.author | Suckling, Keith E. | |
dc.date.accessioned | 2014-06-11T11:00:32Z | |
dc.date.available | 2014-06-11T11:00:32Z | |
dc.date.issued | 1997-09-01 | |
dc.identifier.citation | Berkhout , T , Simon , H M , Jackson , B , Yates , J , Pearce , N , Groot , P H E , Bentzen , C , Niesor , E , Kerns , W D & Suckling , K E 1997 , ' SR-12813 lowers plasma cholesterol in beagle dogs by decreasing cholesterol biosynthesis ' , Atherosclerosis , vol. 133 , no. 2 , pp. 203-212 . https://doi.org/10.1016/S0021-9150(97)00131-7 | |
dc.identifier.issn | 0021-9150 | |
dc.identifier.uri | http://hdl.handle.net/2299/13697 | |
dc.description.abstract | SR-12813 inhibits cholesterol biosynthesis in Hep G2 cells via an enhanced degradation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Here we also show that SR-12813 inhibits cholesterol biosynthesis in vivo. A sterol balance study was performed in normolipemic beagle dogs. The dogs were given SR-12813 orally at dosages of 10 and 25 mg/kg/day for a period of 9 days. After 7 days plasma cholesterol was decreased by 15% in the 10 mg/kg/day group and by 19% in the 25 mg/kg/day group. Using a dual isotope technique no effects on intestinal cholesterol absorption were observed. The sterol balance indicated that endogenous synthesis of cholesterol was reduced by 23% in the 10 mg/kg/day group and by 37% in the 25 mg/kg/day group. Plasma lathosterol-cholesterol levels in dogs treated with 25 mg/kg/day SR-12813 were reduced by 56%, confirming a reduction of the cholesterol biosynthesis. Treatment with SR-12813 or the HMG-CoA reductase inhibitor lovastatin resulted in a large decrease in low density lipoprotein (LDL) cholesterol. It is concluded that SR-12813 reduces cholesterol biosynthesis in the dog model which results in a decrease of bile acid excretion, cholesterol excretion and plasma cholesterol level. The in vivo profile of SR-12813 is very similar to that of direct HMG-CoA reductase inhibitors, although the mode of action of the compound is unique. | en |
dc.format.extent | 10 | |
dc.language.iso | eng | |
dc.relation.ispartof | Atherosclerosis | |
dc.subject | Cholesterol synthesis | |
dc.subject | High density lipoprotein | |
dc.subject | Lathosterol | |
dc.subject | Lovastatin | |
dc.subject | Low density lipoprotein | |
dc.subject | Sitosterol | |
dc.subject | Sterol balance | |
dc.subject | Very low density lipoprotein | |
dc.subject | Cardiology and Cardiovascular Medicine | |
dc.title | SR-12813 lowers plasma cholesterol in beagle dogs by decreasing cholesterol biosynthesis | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Department of Pharmacy | |
dc.contributor.institution | Health & Human Sciences Research Institute | |
dc.contributor.institution | Medicinal and Analytical Chemistry | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1016/S0021-9150(97)00131-7 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |