Effect Of Clofibrate Administration Research Articles

Effect of clofibrate administration on the esterification and deesterification of steroid hormones by liver and extrahepatic tissues in rats

Treatment of rats with clofibrate markedly stimulated the liver microsomal esterification of estradiol, testosterone, pregnenolone, dehydroepiandrosterone, and corticosterone by acyl-CoA:steroid acyltransferase. This enzyme catalyzes the esterification of estradiol with long-chain fatty acids in both liver and extrahepatic tissues. In untreated control rats, brain had the highest acyltransferase activity per milligram of microsomal protein for estradiol esterification (3- to 4-fold higher than in the liver). Although, treatment of rats with clofibrate stimulated the esterification of estradiol by 9- to 14-fold in the liver, estradiol esterification in kidney, lung, brain, uterus, fat, and mammary glands was not increased, indicating that liver may be uniquely sensitive to induction of acyl-CoA:estradiol acyltransferase by clofibrate. In additional studies, esterase activity for hydrolysis of the oleoyl ester of estradiol was determined in control and clofibrate-treated rats. Clofibrate administration increased esterase activity by an average of 107% in fat and 70% in liver. The results indicate that treatment of rats with clofibrate stimulates the hepatic formation of highly lipophilic fatty acid esters that can be hydrolyzed in the liver and in extrahepatic tissues to the parent steroid hormone by a clofibrate-inducible esterase.

Effects of clofibrate on plasma tryptophan, growth hormone, and prolactin and on brain tryptophan and serotonin in prepubertal rats

The effects of clofibrate administration (200 mg/kg, po) on somatic growth, plasma levels of lipids, tryptophan, growth hormone (GH), and prolactin (PRL), as well as on brain concentrations of tryptophan and 5-hydroxytryptamine (5-HT) were studied in prepubertal male rats. The drug did not significantly alter ponderal growth, but an appreciable reduction of tail length was observed in rats treated for 30 days. Triglyceride concentrations in plasma showed a 43% diminution after 30 days of treatment, whereas free fatty acid (FFA) levels were not modified. Clofibrate administration for 7, 15, or 30 days caused a fall in total tryptophan and a significant increase of the free fraction in plasma with no change in brain tryptophan levels. Brain 5-HT was generally unaffected but a marked elevation of this parameter was noted in rats treated for 15 days. Plasma GH and PRL concentrations remained unaltered. It may be concluded from these findings that the slight reduction of somatic growth, the diminution of triglycerides, and the increase of free tryptophan in plasma, induced by chronic clofibrate treatment, are not associated with variations in brain tryptophan and 5-HT levels or with modifications of plasma GH and PRL titers.

Effect of clofibrate administration on several biochemical parameters of normal and thyroidectomized rats

Clofibrate was administered in the diet (0.3%, w/w) for 7 days to normal and thyroidectomized male rats. At the end of the feeding period, the rats were killed by decapitation and several biochemical measurements were made. Inclusion of clofibrate in the diet did not affect weight gain or food consumption of either group of rats. Clofibrate lowered blood serum lipid levels of both normal and thyroidectomized rats, increased liver weight and kidney weight in normal rats and kidney weight in thyroidectomized rats, increased total liver lipid of both normal and thyroidectomized rats. decreased skeletal muscle O 2 consumption and increased liver O 2 consumption, and slightly decreased BMR of normal rats. The primary conclusions are: (1) the hypolipidemic effects of clofibrate do not require thyroxine but are more discernible when thyroxine is present, (2) the clofibrate-induced hypertrophy of liver but not of kidney is thyroxine dependent, and (3) clofibrate alters the O 2 consumption of rat tissues in a counterbalancing manner that results in a minimal effect on BMR.

The Effect of Halofenate or Halofenate Free Acid on Human, Rat and Guinea Pig Platelet Aggregation

Halofenate free acid (HFA), the major metabolite of the hypolipemic agent halofenate, blocked the secondary phase of human platelet aggregation induced by ADP, epinephrine, or thrombin; higher concentrations of clofibrate free acid (CFA) were required to produce similar inhibitory effects on platelet aggregation. HFA and CFA inhibited collagen-induced aggregation of human, rat, or guinea pig platelets. Halofenate orally administered to rats caused inhibition of collagen-induced aggregation when plasma levels of HFA exceeded 300 mug/ml, a clinically achievable human plasma concentration. The platelet inhibitory effects of clofibrate administration were less than those observed with halofenate administration.

Effect of Clofibrate Administration on Heparin-induced Plasma Lipoprotein Lipase Activity in Diabetic Patients with Endogenous Hypertriglyceridemia

Effect of Clofibrate Administration on Heparin-induced Plasma Lipoprotein Lipase Activity in Diabetic Patients with Endogenous Hypertriglyceridemia

Effect of clofibrate administration on plasma post-heparin lipolytic activity in man.

Clofibrate treatment for 15-20 days (1500 mg/day) of diabetic patients with endogenous hypertriglyceridemia produced a significant increase in the plasma post-heparin lipolytic activity. Single administration of the drug (500 mg) did not affect the lipolytic activity though it resulted in an elevation of plasma clofibrate level similarly to the repeated administration for days. The relationship between changes of the lipolytic activity and plasma triglyceride concentration was not fully reciprocal in these patients. It is concluded that clofibrate increases plasma post-heparin lipolytic activity indirectly. However, it remains obscure whether the increase in the activity may have major role in the triglyceride lowering action of the drug.

Effect of clofibrate on lipoprotein metabolism in hyperlipidemic rats.

The effects of clofibrate administration were studied in rats made hyperlipidemic by the feeding of diets high in sucrose. Within 12 hr of administration of clofibrate, there was a marked decrease in the concentration of serum high density lipoproteins but no change in the concentrations of the low and very low density lipoproteins. Between 2-4 days of treatment, the concentration of the very low density lipoproteins decreased whereas that of the low density lipoproteins was unchanged. In addition, the composition of the very low density lipoproteins was altered by clofibrate administration with a decrease in triglyceride and an increase in phospholipid content. The synthesis of high density lipoproteins, as measured by the incorporation of labeled amino acids, decreased within 12 hr of treatment. The synthesis of the very low density lipoproteins was increased during the first 2 days and then decreased slightly. The synthesis of low density lipoproteins did not change. The rate of removal of very low density lipoproteins was measured at various times from 0.5 to 8 days of treatment and was found to be elevated. It was concluded that in the hyperlipidemic sucrose-fed rat, administration of clofibrate results in a reduced level of very low density lipoproteins which may be due in part to enhancement of the rate of removal of this fraction.

Effect of clofibrate administration on the urinary vanilmandelic acid method of Pisano et al.

Effect of clofibrate administration on the urinary vanilmandelic acid method of Pisano et al.