Influence of stress and phenobarbital on corticosterone metabolism during early postnatal life of rat

Erdösová, R; Kraus, Michal; Řehulka, Jiří

doi:10.1016/0024-3205(77)90388-5

Cited by 7 publications

(5 citation statements)

References 27 publications

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“…Our results confirm previous studies in dogs that found no effect of phenobarbital on the ACTHST 18,19 and LDDST. 17 The protocol for the LDDST used in our study is different from the protocols used in studies of human beings, 14,15 which might explain the difference in the respective results. It seems unlikely that phenobarbital treatment for a period exceeding 29 weeks would affect the 2 tests, because all of the cortisol concentrations at week 29 were not different from the respective pretreatment values in these dogs.…”

Section: Adrenal Glandscontrasting

confidence: 41%

“…Phenobarbital also may interfere with the adrenal axis itself by accelerating the metabolism of endogenous steroids. 16,17 Few studies have evaluated possible similar interferences in dogs, 18,19 indicating that the ACTH stimulation test (ACTHST) is not affected by concurrent phenobarbital administration. It is unclear whether or not this is also the case for the LDDST and whether hormonal equilibrium of the adrenal axis is affected by phenobarbital in normal dogs.…”

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confidence: 99%

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Effects of Long‐Term Phenobarbital Treatment on the Thyroid and Adrenal Axis and Adrenal Function Tests in Dogs

Müller¹,

Wolfsheimer²,

Taboada³

et al. 2000

Veterinary Internal Medicne

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Phenobarbital can interfere with the thyroid axis in human beings and rats by accelerating hepatic thyroxine metabolism because of enzyme induction. In human beings, it also can interfere with the low-dose dexamethasone suppression test (LDDST) used to assess adrenal function by accelerating dexamethasone metabolism. This effect can cause a lack of suppression of pituitary ACTH and subsequent adrenal cortisol release after dexamethasone administration. The effects of phenobarbital on the thyroid axis, the adrenal axis, and adrenal function tests were prospectively investigated in 12 normal, adult dogs. Phenobarbital was administered at 5 mg per kilogram of body weight (range, 4.8-6.6 mg/kg) PO q12h for 29 weeks, resulting in therapeutic serum concentrations (20-40 g/mL). Serum total thyroxine (TT4), free thyroxine (FT4) by equilibrium dialysis, total triiodothyronine (TT3), thyrotropin (TSH), and cholesterol were determined before and during phenobarbital treatment. LDDST, ACTH stimulation tests, and ultrasonographic evaluation of the adrenal glands were performed before and during treatment. TT4 and FT4 decreased significantly (P Յ .05), TT3 had minimal fluctuation, TSH had only a delayed compensatory increase, and cholesterol increased during phenobarbital treatment. The delayed increase in TSH, despite persistent hypothyroxinemia, suggests that accelerated hepatic thyroxine elimination may not be the only effect of phenobarbital on the thyroid axis. There was no significant effect of phenobarbital on either of the adrenal function tests. With the methods employed, we did not find any effects of the drug on the hormonal equilibrium of the adrenal axis. Key words: Adrenal axis, Adrenal function tests, Phenobarbital, Thyroid axis. In rats and human beings, anticonvulsant drugs have considerable effects on the thyroid gland and thyroid hormone metabolism. Phenobarbital increases hepatic metabolism and biliary excretion of thyroxine by inducing hepatic enzymes, such as thyroxine-glucuronosyltransferase and cytochrome P450 enzymes. [1][2][3][4][5] In rats, a primary increase of hepatic thyroxine uptake stimulates hepatic deiodinative and excretory processes. Increased fecal and deiodinative clearance of thyroxine and triiodothyronine activates the thyroid axis, resulting in increased pituitary thyrotropin (TSH) secretion and subsequent establishment of a new steady state with normal thyroxine concentrations and somewhat increased TSH concentrations.2,4,6 Thyroid gland weight remains increased, indicating chronic stimulation. 2Several textbooks and review articles in the veterinary literature mention that phenobarbital decreases basal serum thyroxine concentrations in dogs.7-10 However, more recent data suggest that phenobarbital treatment at 30-45 mg q12h for 3 weeks has no significant effect on total thyroxine University, Baton Rouge, LA 70803; email: jtaboada@ mail.vetmed.lsu.edu. Submitted June 26, 1998; Revised March 12, 1999, and July 1, 1999; Accepted October 19, 1999 (TT4), free thyroxine (FT4), and TSH ...

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Section: Adrenal Glandscontrasting

confidence: 41%

mentioning

confidence: 99%

Effects of Long‐Term Phenobarbital Treatment on the Thyroid and Adrenal Axis and Adrenal Function Tests in Dogs

Müller¹,

Wolfsheimer²,

Taboada³

et al. 2000

Veterinary Internal Medicne

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“…Also the finding of a 12 per cent decreased feed consumption per kg body mass gain in Group 3 is worthy of note, even though no valid generalization is possible, since the phenomenon may have been due to sedative action of phenobarbital in the stress produced by venepuncture. No growth-promoting effect of phenobarbital was found in rats (Kritchevsky et al 1976;Erdosova et al 1977).…”

Section: Discussionmentioning

confidence: 83%

“…On the other hand, the concentration of 17-0HCS in the blood plasma of experimental piglets was reduced in the first three groups as against the controls, but the difference was not significant. In contrast, administration of phenobarbital to 4-day-old rats was followed by a rise in corticosterone concentration which was accounted for by low metabolizing activity of the liver at this age (Erdosova et al 1977). That the circulating eosinophile granulocyte counts of the experimental piglets were not always in keeping with the corticosteroid level can be explained by the fact that newborn piglets have low eosinophil counts in general.…”

Section: Discussionmentioning

confidence: 86%

“…In newborn piglets receiving higher doses and killed after a shorter period of time this effect was only suggested. Hepatomegalic action of phenobarbital in laboratory animals was repeatedly demonstrated (Kritchevsky et al 1976;Erdosova et al 1977), together with an increased content of hepatic lipids (Tuma et al 1974). The concentration of liver glycogen in adult rats treated with phenobarbital was reduced (J apundzic et al 1969).…”

Section: Discussionmentioning

confidence: 99%

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Effect of Phenobarbital on Growth, Adrenocortical Activity and Some Metabolic Parameters in Piglets

Dvorák¹

1979

Acta Vet. Brno

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Long-lasting effects of early barbiturates on central nervous system and behavior

Fishman

Yanai

1983

Neuroscience & Biobehavioral Reviews

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Influence of stress and phenobarbital on corticosterone metabolism during early postnatal life of rat

Cited by 7 publications

References 27 publications

Effects of Long‐Term Phenobarbital Treatment on the Thyroid and Adrenal Axis and Adrenal Function Tests in Dogs

Effects of Long‐Term Phenobarbital Treatment on the Thyroid and Adrenal Axis and Adrenal Function Tests in Dogs

Effect of Phenobarbital on Growth, Adrenocortical Activity and Some Metabolic Parameters in Piglets

Long-lasting effects of early barbiturates on central nervous system and behavior

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