Differential effect of clofibrate on inflammation-induced alterations in plasma proteins in the rat.
Daily intramuscular injections of clofibrate begun 6h before the initiation of inflammation induced by the subcutaneous injection of turpentine exerted a differential, dose-dependent inhibition of the anticipated acute-phase globulin response. Specifically, clofibrate at 140mg/kg muted the increase in alpha(2)-macrofoetoprotein, but did not affect that of seromucoid or haptoglobin and only transiently inhibited the rise in copper and the rebound in transferrin. A higher dose, 280mg/kg, markedly suppressed alpha(2)-macrofoetoprotein appearance and the rebound in transferrin, somewhat inhibited the increase in seromucoid and haptoglobin and only transiently affected the rise in plasma copper; 420mg of clofibrate/kg very nearly abolished the appearance of alpha(2)-macrofoetoprotein, markedly suppressed the transferrin rebound and the increases in seromucoid and haptoglobin and again only transiently affected the increase in copper. Clofibrate did not diminish the localized inflammatory response, did not cause microscopically detectable liver damage and did not prevent the hypozincaemia, hypoalbuminaemia and enhanced amino acid uptake by liver usually associated with inflammation. Thus it is unlikely that clofibrate exerted its dose-dependent selective inhibition by muting the initial stimulus or by impairing hepatic metabolism. This seemingly selective action of clofibrate on plasma-protein alterations during inflammation may provide a means of elucidating the function of individual acute-phase globulin during disease. Clofibrate of itself, apart from inflammation, produced decreases in plasma zinc, copper, transferrin and seromucoid and an increase in hepatic amino acid uptake that were to some extent dependent on the dose of the drug.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002994:Clofibrate / Q000494:pharmacology*; D003300:Copper / Q000097:blood; D007249:Inflammation / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D015032:Zinc / Q000097:blood; D000511:alpha-Macroglobulins / Q000378:metabolism
D000596:Amino Acids; D001798:Blood Proteins; D012709:Serum Albumin; D014168:Transferrin; D000511:alpha-Macroglobulins; D003300:Copper; D002994:Clofibrate; D015032:Zinc