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  • Title: Effect of clofibrate treatment on hepatic prostaglandin catabolism and action.
    Author: Brass EP, Ruff LJ.
    Journal: J Pharmacol Exp Ther; 1991 Jun; 257(3):1034-8. PubMed ID: 2046019.
    Abstract:
    Prostaglandins (PG) modulate hepatocyte glucose and lipid metabolism. Hepatocytes rapidly metabolize PG via beta-oxidation, terminating PG action. Clofibrate induces hepatic peroxisomal beta-oxidative activity, for which PG are substrates. To determine the effect of clofibrate-treatment on liver PG metabolism and action, hepatocytes were isolated from rats maintained on a control or clofibrate-supplemented (0.5%) diet for 7 to 9 days. Rates of PG catabolism were determined by high performance liquid chromatography resolution of [3H]PG from [3H]metabolites. Clofibrate treatment enhanced the rates of PGE2, PGF2, and PGD2 degradation by 85%, 278% and 137%, respectively. Rates of PG degradation were correlated with hepatocyte carnitine acetyltransferase activity, a marker of peroxisomal proliferation. Further evidence of enhanced hepatocyte peroxisomal beta-oxidation of PG after clofibrate-treatment was obtained by confirming loss of the 1-position carbon from [1-14C]PGE2 during PGE2 metabolism and failure of the carnitine acyltransferase inhibitor acetyl-DL-aminocarnitine to inhibit PGE2 metabolism. Associated with the faster degradation of PGE2 by hepatocytes from clofibrate-treated rats was loss of inhibition of hepatocyte glucagon-stimulated glycogenolysis by exogenous PGE2. Thus, clofibrate's induction of peroxisomal beta-oxidation is associated with accelerated catabolism of PG and decreased PG action. Alterations in PG breakdown provide a mechanism for modulating hepatic PG effects.
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