Phenobarbital-induced Alterations in the Metabolism of [3H]Vitamin D3 by the Perfused Rachitic Rat Liver In Vitro

Baran, Daniel T.; Fausto, Aurora; Roberts, Marilyn L.; Karl, Irene E.; Avioli, Louis V.

doi:10.1172/jci109550

Cited by 15 publications

(9 citation statements)

References 26 publications

(35 reference statements)

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“…The percentage of total radioactivity remaining as ~H-vitamin D or appearing as 3H-25OHD in the perfusate during the course of the 3 h perfusion was determined and converted to pmol. The identity of the 3H-25OI-ID obtained from the Sephadex LH-20 columns has previously been confirmed by high pressure liquid chromatography and UV absorbance at 263 nm [14] and was substantiated in these studies by comigration with authentic 25OHD (Upjohn Co) and 3H-25OHD (Amersham Co) on Sephadex LH 20.…”

Section: Methodssupporting

confidence: 55%

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1,25 dihydroxyvitamin d-induced inhibition of3H-25 hydroxyvitamin D production by the rachitic rat liverin vitro

Baran

Milne

1983

Calcif Tissue Int

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The effect of the vitamin D metabolites 1,25 dihydroxyvitamin D (100 pg/ml) and 25-hydroxyvitamin D (30 ng/ml) on hepatic production of 3H-25 hydroxyvitamin D was investigated using rachitic liver perfusions and homogenates. 1,25 dihydroxyvitamin D inhibited hepatic 3H-25 hydroxyvitamin D production in the liver perfusion (3.6 +/- 0.4 vs 2.0 +/- 0.5 pmol/liver, P less than 0.05) and in liver homogenates (11.9 +/- 0.6 vs 10.1 +/- 0.4 pmol/g liver protein/3 h, P less than 0.02). Inhibition was time and dose dependent. 25-hydroxyvitamin D inhibited production in liver homogenates (11.9 +/- 0.6 vs 9.2 +/- 0.1 pmol/g liver protein/3 h, P less than 0.05) but not in the intact liver (3.6 +/- 0.4 vs 3.4 +/- 0.5 pmol/liver). The data indicate that 1,25 dihydroxyvitamin D is able to feedback regulate the production of its precursor, 25-hydroxyvitamin D. Although 25-hydroxyvitamin D also inhibits its own production in liver homogenates, it failed to alter total production in the intact liver, suggesting that this metabolite may require immediate access to the vitamin D 25-hydroxylase, located on the microsomes and mitochondria, to induce inhibition.

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Section: Methodssupporting

confidence: 55%

“…The surgical removal and perfusion of the livers were per-formed as described [14]. Under light ether anesthesia, the esophagus was ligated and cut.…”

Section: Methodsmentioning

confidence: 99%

1,25 dihydroxyvitamin d-induced inhibition of3H-25 hydroxyvitamin D production by the rachitic rat liverin vitro

Baran

Milne

1983

Calcif Tissue Int

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“…Livers were perfused with reconstituted blood [KrebsRinger bicarbonate-plasma-red blood cells (3:1:1)] obtained from rachitic nondiabetic rats reared on the same diet. The surgical removal and perfusion of the livers were performed as described previously (17)(18)(19). The esophagus, hepatic artery, and inferior vena cava were ligated; the bile duct, portal vein, and superior vena cava were cannulated; and the liver was perfused through the portal vein.…”

Section: Isolated Liver Perfusions: In Vitro Evaluation Of Hepatic VImentioning

confidence: 99%

Vitamin D Metabolism in the Chronic Streptozotocin-Induced Diabetic Rat*

et al. 1983

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Alterations in circulating vitamin D3 metabolites have been documented in both experimental and human diabetes mellitus. Using a recirculating hepatic perfusion system and in vitro kidney mitochondrial assays, we studied vitamin D3 hydroxylation in control and insulin-deficient rats 6 weeks after the induction of streptozotocin-diabetes. Vitamin D3-25-hydroxylase activity, assessed by hepatic conversion of [3H]vitamin D3 to [3H]25-hydroxyvitamin D3 during a 4-h perfusion, was similar in diabetic and control animals. The hepatic degradation of 25-hydroxyvitamin D3 to more polar metabolites was also normal, as was glucuronide conjugation and biliary excretion of vitamin D3 metabolites. The chronic insulin-deficient state resulted in a significantly (P less than 0.01) decreased 1 alpha-hydroxylase activity and enhanced (P less than 0.001) renal 24-hydroxylase activity. These alterations in vitamin D metabolism may relate to the deranged mineral homeostasis and skeletal morphology observed in rats and humans with chronic insulin deficiency.

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“…Moreover, increased in vitro production of 25OHDa has been reported in perfused livers of rats treated with phenobarbital for 5 days [36]. Perhaps the most plausible explanation for the subsequent decline in serum 25OHD concentration in phenobarbital-treated animals would be a combination of increased degradation of 25OHD and decreased availability of vitamin D substrate.…”

Section: Discussionmentioning

confidence: 98%

Sequential changes in mineral metabolism and serum vitamin D metabolite concentrations produced by phenobarbital administration in the rat

Hahn

Halstead

1983

Calcif Tissue Int

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Summary.We examined the effect of daily phenobarbital administration on serum vitamin D metabolite levels and indices of vitamin D biologic activity in 7-week-old male rats maintained on parenteral vitamin D supplementation (125 ng/day). Treatment with phenobarbital (75 mg/kg/day) produced a biphasic response in parameters of vitamin D biologic effect, including serum calcium concentration, serum inorganic phosphate concentration, and intestinal 4'~Ca calcium absorption. An initial increase in these values, maximal after 3-5 days of treatment, was followed by a subsequent decline to subnormal levels by day 21. A parallel biphasic pattern was observed for serum 25-hydroxyvitamin D (25OHD) concentration. Serum 25OHD reached a peak increase of 87% above control levels (P < 0.0l), observed after 5 days of treatment, and subsequently declined to 62% of control animal values (P < 0.01) by 21 days. Serum 24,25(OH)._,D concentration followed a similar course and exhibited a strong positive correlation w/th serum 25OHD concentrations (r = 0.74, P < 0.01). In contrast, serum 1,25(OH)~_D concentration was not significantly different from control values after 5 days but was increased 80% over control values (P < 0.05) by day 21. Serum vitamin D concentration declined progressively in treated animals, falling to 50% of control levels (P < 0.05) by day 5 and to 27% of control levels (P < 0.001) by day 21. At the point of maximal increase in serum 25OHD concentration, hepatic microsomal vitamin D3-25-hydroxylase activity was not increased in the treated animals whereas hepatic mitochondrial vitamin D3-25-hydroxylase activity was increased by 2.4-fold. Increased hepatic mitochondrial vitamin D3-25-hydroxylase activity persisted through 21 days of phenobarbital treatment. It is concluded that phenobarbital ad-

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Phenobarbital-induced Alterations in the Metabolism of [3H]Vitamin D3 by the Perfused Rachitic Rat Liver In Vitro

Abstract: A B S T R A C T Anticonvulsant therapy of seizure disorders in man is

Cited by 15 publications

References 26 publications

1,25 dihydroxyvitamin d-induced inhibition of3H-25 hydroxyvitamin D production by the rachitic rat liverin vitro

1,25 dihydroxyvitamin d-induced inhibition of3H-25 hydroxyvitamin D production by the rachitic rat liverin vitro

Vitamin D Metabolism in the Chronic Streptozotocin-Induced Diabetic Rat*

Sequential changes in mineral metabolism and serum vitamin D metabolite concentrations produced by phenobarbital administration in the rat

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