The effects of p-chlorophenoxyisobutyrate on the turnover rate and distribution of thyroid hormone in the rat

Ruegamer, W. R.; Ryan, N. Thomas; Richert, Dan A.; Westerfeld, W. W.

doi:10.1016/0006-2952(69)90086-0

Cited by 37 publications

(8 citation statements)

References 15 publications

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“…Glycerol phosphate dehydrogenase activity is present both in the particulate and in the soluble fractions. Although the activity in the particulate fraction is not coenzyme-dependent (Dewan & Green, 1937), that in the supernatant fraction is dependent on NADI (Baranowski, 1949 al., 1968;Ruegamer et al, 1969). Table 2 indicate that both clofibrate and clofenapate increased the specific activity of glycerol phosphate dehydrogenase in the homogenate and the total activity in the liver almost to the same extent.…”

Section: Glycerol Phosphate Dehydrogenasementioning

confidence: 99%

“…Both catalase and glycerol phosphate dehydrogenase are present in the cytosol as well as in the mitochondria of liver. In studies reported so far on the drug-induced increase in the activities of these two enzymes, attention was confined to the total enzyme activity in liver homogenates without considering its intracellular distribution (Ruegamer et al, 1969;Reddy et al, 1971). It was reported from our laboratory that administration of clofibrate to the rat increased the content of hepatic mitochondria by 50-100 % (Kurup et al, 1970).…”

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confidence: 99%

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Increase in hepatic catalase and glycerol phosphate dehydrogenase activities on administration of clofibrate and clofenapate to the rat

Krishnakantha

Kurup

1972

Biochemical Journal

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1. Clofenapate (methyl 2-[4-(p-chlorophenyl)phenoxy]-2-methylpropionate) fed to the rat in the diet increased the content of mitochondrial protein in the liver by 50-60%. In this respect it resembled the related compound clofibrate (ethyl alpha-p-chlorophenoxyisobutyrate), which is widely used as an antihypercholesterolaemic drug. 2. Both compounds when fed to the rat enhanced the activity of alpha-glycerol phosphate dehydrogenase in the liver mitochondria manyfold, but were without effect on the enzyme in the soluble fraction. 3. On the other hand, the catalase activity in the supernatant fraction increased twofold after administration of the drugs. The mitochondrial catalase activity showed a consistent decrease. 4. It was unlikely that under the influence of the drug the increase in catalase activity took place in the mitochondrial particles and was leached into the cytosol during isolation. 5. The increase in catalase activity in the cytosol under the influence of the drug is best explained on the assumption that peroxisomes which contain this enzyme, and which are known to increase on administration of the drug, were broken during the process of cellular fractionation and released the enzyme into the cytosol. 6. All the above effects shown by both drugs were fully reversed when drugs were withdrawn from the diet. 7. Clofenapate was effective in bringing about the above changes when administered to the animal at one-hundredth the concentration of clofibrate.

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Section: Glycerol Phosphate Dehydrogenasementioning

confidence: 99%

mentioning

confidence: 99%

Increase in hepatic catalase and glycerol phosphate dehydrogenase activities on administration of clofibrate and clofenapate to the rat

Krishnakantha

Kurup

1972

Biochemical Journal

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“…The possible implication of thyroid hormone in the hypolipidaemic action of phenoxyisobutyrate (fibrate) drugs has been suggested by the finding that clofibrate stimulates liver mitochondrial a~-glycerophosphate dehydrogenase activity, a classical thyromimetic response [1]. Observations of a drug-induced increase in hepatic uptake of thyroxine (I"4") have been interpreted in support of this view [1].…”

mentioning

confidence: 99%

Differential expression and ciprofibrate induction of hepatic UDP-glucuronyltransferases for thyroxine and triiodothyronine in Fischer rats

Visser

Kaptein

Harpur³

1991

Biochemical Pharmacology

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“…Alternatively clofibrate might affect hepatic protein synthesis indirectly by its effect on amino acid availability, hormones or adenylate cyclase (Ruegamer et al, 1969;Greene et al, 1970;Fulton & Hsia, 1972;Fedele et al, 1976). If amino acid availability does exert some regulatory effect on hepatic synthesis of plasma proteins (Rothschild et al, 1969;Morgan & Peters, 1971), the fact that clofibrate enhances amino acid flux into liver should stimulate rather than depress plasma protein production.…”

Section: Tementioning

confidence: 99%

Differential effect of clofibrate on inflammation-induced alterations in plasma proteins in the rat

Powanda

Abeles

Bostian

et al. 1979

Biochemical Journal

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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.

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The effects of p-chlorophenoxyisobutyrate on the turnover rate and distribution of thyroid hormone in the rat

Cited by 37 publications

References 15 publications

Increase in hepatic catalase and glycerol phosphate dehydrogenase activities on administration of clofibrate and clofenapate to the rat

Increase in hepatic catalase and glycerol phosphate dehydrogenase activities on administration of clofibrate and clofenapate to the rat

Differential expression and ciprofibrate induction of hepatic UDP-glucuronyltransferases for thyroxine and triiodothyronine in Fischer rats

Differential effect of clofibrate on inflammation-induced alterations in plasma proteins in the rat

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