Hypolipidemic activity of some hydropolyborate salts in rodents.
A series of hydropolyborate salts were observed to possess hypolipidemic activity in rodents. Tetramethylammonium octahydrotriborate, tetramethylammonium hexahydrohexaborate, tetramethylammonium dodecahydrododecaborate and triethyl-ammonium dodecahydrododecaborate proved to be very effective in lowering serum cholesterol and triglyceride levels in CF1 mice, i.p. and Sprague Dawley rats, orally. Tissue lipids were reduced by these agents e.g. liver cholesterol, and triglyceride and small intestine mucosa cholesterol levels. [3H] Cholesterol distribution studies confirm that steroid levels are lower in most major tissues. The rat serum lipoprotein lipid content was altered by drug treatment, with cholesterol and triglyceride being reduced in the VLDL and cholesterol being reduced in the LDL. HDL cholesterol levels were elevated by drug treatment. The fecal lipids were increased with select derivatives. The enzyme activities involved in de novo synthesis of hepatic lipids were affected by the hydropolyborate salts including cytoplasmic ATP-dependent citrate lyase, acetyl CoA synthetase, acyl CoA cholesterol acyl transferase, sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
Brotherton
R J
RJ
Docks
E L
EL
Griffin
T S
TS
Sood
A
A
Spielvogel
B F
BF
D000818:Animals; D001011:Aorta / Q000737:chemistry; D001881:Borates / Q000494:pharmacology*; D002784:Cholesterol / Q000737:chemistry; D005243:Feces / Q000737:chemistry; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007421:Intestine, Small / Q000737:chemistry; D008074:Lipoproteins / Q000737:chemistry; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains
D001881:Borates; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D002784:Cholesterol