Suppression of acute-phase synthesis of fibrinogen by a hypolipidemic drug (clofibrate).
The effect of pretreatment of rats with a hypolipidemic agent, clofibrate ethyl alpha-(p-chlorophenoxy)isobutyrate on the acute-phase induction of fibrinogen synthesis by thrombin injections was evaluated. Rats were pretreated with graded dosages of clofibrate (10-300 mg/kg day), then injected intraperitoneally with 1,000 U topical thrombin at 0 hours and at 24 hours to induce an acute-phase induction of fibrinogen synthesis. In control rats, thrombin injections rapidly diminished plasma fibrinogen levels and induced a marked rise in serum free fatty acids. However, by 48 hours after the initial injection, fibrinogen biosynthesis increased 5.6 fold and plasma levels were elevated twofold above normal. In contrast, clofibrate pretreatment of rats markedly attenuated both the thrombin-induced free fatty acid mobilization and the subsequent stimulation of fibrinogen synthesis. The optimal dosage of clofibrate which blocked the effect of thrombin of fibrinogen synthesis was 100 mg/kg day. These results suggest that the injection of acute-phase enhancements of fibrinogen synthesis is mediated by prior alterations in free fatty acid metabolism and that hypolipidemic drugs which block FFA mobilization will also suppress acute-phase fibrinogen hyperproduction.
D000818:Animals; D002994:Clofibrate / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005340:Fibrinogen / Q000096:biosynthesis*; D008297:Male; D051381:Rats; D013917:Thrombin / Q000494:pharmacology
D005230:Fatty Acids, Nonesterified; D005340:Fibrinogen; D013917:Thrombin; D002994:Clofibrate