Differential effects of fibrates on the acyl composition of microsomal phospholipids in rats.
1. The time-course and comparative effects of treatment with clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on the acyl composition of the main microsomal phospholipids, i.e. phosphatidylcholine and phosphatidylethanolamine, have been studied in male Sprague-Dawley rats. 2. The administration of the three fibrates caused a strong peroxisomal induction and a hypolipidaemic effect. Concerning the changes in acyl composition, CFB and BFB behaved in a similar way, with differences which could be attributed to their different potency as peroxisome inducers, whereas GFB showed a somewhat distinct profile. 3. The three drugs increased the relative content of palmitic, palmitoleic and oleic acids, whereas the levels of stearic acid and also those of long chain, highly unsaturated fatty acids docosatetraenoic, docosapentaenoic and docosahexaenoic acids were reduced. In general, these effects appeared from the first day of treatment and were highly correlated with peroxisomal proliferation. In addition, they were more evident in the phosphatidylcholine than in the phosphatidylethanolamine fraction. 4. Fibrates increased total monounsaturated fatty acids, whereas a decrease in total polyunsaturated fatty acids in the phosphatidylcholine fraction was observed in CFB- and BFB-, but not in GFB-treated rats. Clear differences appeared between CFB and BFB on the one hand, and GFB on the other when the influence of fibrate treatment on the molar percentages of linoleic, eicosatrienoic, arachidonic and mead acids was analyzed. 5. GFB increased linoleic acid content in phosphatidylethanolamine, whereas CFB and BFB decreased its level in both phospholipid fractions. In contrast, CFB and BFB enhanced eicosatrienoic and mead acids in both fractions and arachidonic acid in phosphatidylethanolamine, whereas GFB had practically no effect.
Vázquez
M
M
Dept. Farmacología y Química Terapeutica, Facultad de Farmacia, Núcleo Universitario de Pedralbes, Barcelona, Spain.
Muñoz
S
S
Alegret
M
M
Adzet
T
T
Merlos
M
M
Laguna
J C
JC
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002994:Clofibrate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000378:metabolism*; D015248:Gemfibrozil / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D008830:Microbodies / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005231:Fatty Acids, Unsaturated; D000960:Hypolipidemic Agents; D008055:Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D002994:Clofibrate; D015248:Gemfibrozil; D001629:Bezafibrate