The effects of boron hypolipidemic agents on LDL and HDL receptor binding and related enzyme activities of rat hepatocytes, aorta cells and human fibroblasts.
Two boron-containing hypolipidemic agents, N,N-dimethyl-n-octadecylamine borane and tetrakis-mu-(trimethylamine-boranecarboxylato)bis-(trimethylamine- carboxyborane)-dicopper(II) were shown to reduce significantly serum cholesterol and triglyceride levels after 14 days administration in rats. Serum low density lipoprotein (LDL) cholesterol content was reduced by both agents; however, high density lipoprotein (HDL) cholesterol was elevated by N,N-dimethyl-n-octadecylamine borane but reduced by the dicopper (II) complex. The boron agents suppressed LDL binding and internalization in hepatocytes, fibroblasts and aorta cells and elevated HDL binding and degradation in hepatocytes. Enzyme activities were modulated by the boron derivatives which would favor less cholesterol deposition in peripheral tissues and further clearance from the plaque cells.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Spielvogel
B F
BF
Griffin
T S
TS
Docks
E L
EL
Brotherton
R J
RJ
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000201:enzymology; D001895:Boron / Q000494:pharmacology*; D002352:Carrier Proteins; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D016601:RNA-Binding Proteins; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D011973:Receptors, LDL / Q000187:drug effects* / Q000378:metabolism; D018110:Receptors, Lipoprotein
D002352:Carrier Proteins; D000960:Hypolipidemic Agents; D008055:Lipids; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein; D001895:Boron