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Quantitative requirement for cholecalciferol in the absence of ultraviolet light.

Studies were conducted to determine the basic requirement of the bird for cholecalciferol in the absence of ultraviolet light by utilizing filter sleeves on fluorescent lights in the room and brooder. In Experiment 1, some pens were fitted with filter tubes and some lights were turned off. All the birds received a cholecalciferol-deficient diet. Birds with ultraviolet light excluded grew slowly, developed rickets (95%), had low plasma calcium, and low bone ash (27%); whereas birds exposed to the fluorescent light had normal growth and plasma calcium, slightly low bone ash (38%), and some rickets (12%). Experiments 2 and 3 were conducted to determine the amount of cholecalciferol that must be added to the diet under conditions in which ultraviolet light was excluded. In Experiment 2, the highest level of cholecalciferol fed was 400 ICU/kg. This level was not sufficient to permit the chickens to have weight gain or bone ash equal to the birds receiving the ultraviolet light. The birds receiving 400 ICU/kg of diet also had a 77% incidence of rickets compared with 20% for the birds receiving ultraviolet lights. In Experiment 3, when birds received 800 or 1,600 ICU/kg of cholecalciferol in the diet, they grew and were comparable to those receiving ultraviolet light for the criteria measured.

Animals↗

Cardiovascular risk factors during estrogen-norethindrone and cholecalciferol treatment.

The effect of cholecalciferol and estrogen-norethindrone treatment on total cholesterol level, high-density lipoprotein cholesterol level, blood pressure, and body mass index was investigated in 74 postmenopausal women in a double-blind, randomized trial. Blood pressure and body mass index did not change throughout the study. We demonstrated a decrease (11%) in serum cholesterol level after 1 year of treatment with estrogen-norethindrone. When this treatment was combined with cholecalciferol, a similar decrease (13%) was observed. The hypocholesterolemic effect was correlated to body mass index in a way that indicated the most pronounced decrease in lean women. The high-density lipoprotein cholesterol/total cholesterol fraction increased by 45% after 1 year of estrogen-norethindrone treatment, while an increase of 25% after 1 year was seen when cholecalciferol was added to the treatment. The latter increase was not different from a similar increase in the placebo group. The possible dyslipidemic effect of cholecalciferol, along with the risk of hypercalcemia, emphasizes the caution necessary in cholecalciferol treatment.

Aged↗

Elevated 25-hydroxy and normal 1,25-dihydroxy cholecalciferol serum concentrations in a successfully-treated case of vitamin D3 toxicosis in a dog.

A 4-y old, 27 kg spayed female German Shepherd dog was observed to ingest one 1-oz package of a rodenticide containing cholecalciferol. An initial serum calcium concentration of 15.7 mg/dl was successfully reduced to normal during 10 d using calcitonin and prednisolone. During that time, the serum 25-hydroxy and 1,25-dihydroxy cholecalciferol concentrations ranged from 637 to 315 ng/ml (normal 32 +/- 6 ng/ml) and 64 to 29 pg/ml (normal 34 +/- 19 pg/ml), respectively. Serum mid-molecule parathyroid hormone concentrations (76 to 97 pcmol/L) were within the normal range (85-140 pcmol/L). These data indicate that hypercalcemia seen in dogs following field exposures to cholecalciferol-containing rodenticides may be associated with elevated 25-hydroxy rather than 1,25-dihydroxy cholecalciferol. Consequently, serum 25-hydroxy cholecalciferol concentrations may be the most conclusive method for diagnosing hypervitaminosis D3 toxicosis in the live dog.

Animals↗

Cholecalciferol treatment restores the relaxant responses of spontaneously hypertensive rat arteries to bradykinin.

The vasodilation and hyperpolarization induced by bradykinin (BK) in the mesenteric vascular bed and mesenteric arteries from spontaneously hypertensive rats (SHR) and from normotensive Wistar rats (NWR), as well as Wistar Kyoto rats (WKY), was investigated before and after prolonged oral treatment with cholecalciferol (125 mg kg(-1) body weight per day) for 3 weeks. The cholecalciferol treatment caused a decrease in the SHR blood pressure, as well as a normalization in the resting potential of the smooth muscle cell membrane of mesenteric arteries and restored their hyperpolarizing response to BK. The concentration-response curves for the vasodilator effect of BK on the mesenteric vascular bed were significantly decreased in SHR and in WKY when compared with NWR. Cholecalciferol treatment improved the maximum responses of the SHR preparation, bringing them to levels similar to those of the NWR preparations, which themselves were unaffected by the treatment. In the presence of apamin, a Ca(2+)-dependent K(+) channel inhibitor, the maximum responses to BK in preparations from NWR or cholecalciferol-treated SHR decreased to values similar to those observed in untreated SHR. Our results indicate that the low responsivity of the SHR resistance vessels to the relaxant effect of BK is due to impaired Ca(2+)-dependent K(+) channels and that reversion of this impairment contributes to the blood pressure reduction caused by the cholecalciferol treatment. However, the mechanism of the low responsivity in WKY remains to be investigated.

Journal Article↗

Cholecalciferol modulates plasma phosphate but not plasma vitamin D levels and intestinal phosphate absorption in rainbow trout (Oncorhynchus mykiss).

Since the vitamin D endocrine system modulates phosphorus homeostasis and regulates inorganic phosphate (Pi) uptake by the small intestine in mammals and birds, we determined the effects of dietary cholecalciferol (vitamin D3) on Pi uptake by the small intestine, Pi concentrations in the plasma, Pi concentrations in the intestinal lumen, intestinal weights, liver weights, and concentrations of vitamin D metabolites in the plasma of rainbow trout (Oncorhynchus mykiss) fed phosphorus-sufficient (0.6 g/100 g) diets. Five groups of trout initially weighing 55.8 +/- 0.6 g were fed purified diets containing 0, 300, 2,500, 10,000, and 40,000 IU vitamin D3/kg diet over a 7- to 8-day feeding period. Plasma Pi concentration was higher in trout fed 2,500-40,000 IU/kg diet (8.26 +/- 0.27 mmol/L) than in those fed 0 and 300 IU/kg (6.99 +/- 0.30). Liver weights were 30-50% greater in fish fed 0 IU/kg than in those fed 300-40,000 IU/kg. There were no significant, diet-related differences in plasma levels of 25-hydroxycholecalciferol [25(OH)D3] and 1,25 dihydroxycholecalciferol [1,25(OH)2D3]. Increasing levels of dietary cholecalciferol also did not enhance in vitro Pi uptakes by the intestine (range of means: 0.22-0.29 nmol/mg tissue. min) and Pi concentrations in the intestinal lumen (8.5-13.5 mmol/L). Pi uptake did not differ among tissues incubated in vitamin D3, 25(OH)D3, or 1,25(OH)2D3. These results demonstrate that when fish are fed P-sufficient diets, dietary cholecalciferol increases plasma Pi concentrations but decreases liver weights, alterations which are not accompanied by changes in intestinal weight, Pi uptake by the intestine, Pi concentration in the intestinal lumen, and circulating metabolites of cholecalciferol.

Animals↗

The intracellular distribution of [1-3H]cholecalciferol in the intestine of vitamin D-deficient and -supplemented rats.

1. [1-(3)H]Cholecalciferol was administered orally at two dosages to vitamin D-deficient and -supplemented rats, and the intracellular distribution of the vitamin in the intestinal mucosa studied. 2. The concentration of cholecalciferol was highest in a fraction consisting of brush borders and nuclei. The microsomal fraction contained a higher concentration of the vitamin than the mitochondrial fraction in deficient rats, irrespective of the dose, whereas in the vitamin D-supplemented rats the concentration was the same in the two fractions. 3. Appreciable metabolism of the cholecalciferol occurred only in the supplemented rats and the metabolites were found predominantly in the mitochondrial fraction. 4. The cholecalciferol is more tightly bound to the microsomal fraction than to the mitochondrial fraction. 5. Experiments conducted in vitro have shown that all the intracellular particles combine with the vitamin either when dissolved in ethanol or bound to albumin. However, such an uptake does not account for the high concentration of radioactivity found in vivo in the fraction containing nuclei and brush border, nor for the tightly bound vitamin in the microsomal fraction.

Animals↗

The metabolism of cholecalciferol in the liver of Japanese quail (Coturnix coturnix japonica) with particular reference to the effects of oestrogen.

1. Studies were carried out in vitro with the livers of Japanese quail that had been fed from hatching on diets supplying their full requirements for vitamin D. 2. 25-Hydroxycholecalciferol was the major metabolite when liver homogenates of egg-laying female and oestrogen-treated quail of both sexes were incubated with [3H]cholecalciferol. 3. Very little 25-hydroxycholecalciferol was generated from liver homogenates of adult male and immature quail. Instead the cholecalciferol was converted into one or more compounds less polar than 25-hydroxycholecalciferol and into a number of highly polar metabolites, some of which were water-soluble. 4. Oestrogen not only stimulated the 25-hydroxylation of cholecalciferol but also protected both cholecalciferol and 25-hydroxycholecalciferol from degradation by the enzymic pathways active in immature and male birds. 5. These actions of oestrogen may be of physiological significance in relation to the high requirements of laying birds for 1,25-dihydroxycholecalciferol to support the intense metabolism of calcium associated with egg-shell calcification.

Aging↗

Discrimination in the metabolism of orally dosed ergocalciferol and cholecalciferol by the pig, rat and chick.

Vitamin D-deficient pigs, rats and chicks were repleted with four daily oral doses of crystalline ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) containing equal concentrations of each. At 24 h after the last dose, the plasma of each species was analysed for vitamin D and 25-hydroxyvitamin D by standard methods. The mean (+/- S.D.) ratios of plasma cholecalciferol to ergocalciferol concentration were 1.5 +/- 0.1 (pig). 1.7 +/- 0.1 (rat) and 6.3 +/- 1.2 (chick). The mean ratios of plasma 25-hydroxycholecalciferol to 25-hydroxyergocalciferol concentration were 4.0 +/- 0.1 (pig), 0.4 +/- 0.02 (rat) and 10.7 +/- 3.4 (chick). The mean plasma cholecalciferol/ergocalciferol ratios for the 24,25-dihydroxy-, 25,26-dihydroxy- and 1,25-dihydroxy-derivatives in the pig were 2.6 +/- 0.6, 5.8 +/- 1.3 and 5.8 +/- 0.8 respectively. This is the first evidence that mammals other than the New World monkey, like birds, discriminate between ergocalciferol and cholecalciferol. These data, therefore, suggest that species discrimination between the different forms of vitamin D is probably a general phenomenon in mammals. Moreover, this is the first indication of a species (rat) that discriminates against a cholecalciferol metabolite in favour of an ergocalciferol metabolite. Species discrimination against particular forms of vitamin D may be important to the choice of experimental animal models for studying the regulation of vitamin D metabolism and may also be an important consideration in dietary vitamin supplementation.

25-Hydroxyvitamin D 2↗

Sex differences in the hydroxylation of cholecalciferol and of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol in rat liver.

The effect of sex hormones on hydroxylation of cholecalciferol ('vitamin D3') and of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol has been investigated in female- and male-rat livers. The mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities were respectively 4.6- and 2.7-fold higher in female- than in male-rat livers. The microsomal 1 alpha-hydroxycholecalciferol 25-hydroxylase was 2.8-fold higher in male- than in female-rat liver. No significant difference was found in the microsomal 25-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. Liver microsomes (microsomal fractions) from male, but not from female, rats also catalysed 1-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. Injection of testosterone into female rats decreased the mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities, but not to a statistically significant extent. Testosterone treatment had no effect on the microsomal hydroxylases in female-rat liver. Injection of oestradiol valerate to male rats resulted in increased activities of both mitochondrial hydroxylases to the same levels as those of control females, while the microsomal enzyme activities decreased. The present results indicate that sex hormones exert a regulatory control on the mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities.

Animals↗

Dietary cholecalciferol and phosphorus influence intestinal mucosa phytase activity in broiler chicks.

1. The role of cholecalciferol and phosphorus in the regulation of intestinal mucosa phytase was investigated in broiler chicks. 2. A total of 144 7-d-old male broiler chicks were grouped by weight into 6 blocks of 4 cages with 6 broiler chicks per cage. Four maize-soybean meal-based mash diets were randomly assigned to cages within each block. The 4 diets consisted of cholecalciferol at 0 or 75 microg/kg and total phosphorus at 3.6 or 7.0 g/kg in a 2 x 2 factorial arrangement. The birds were given the experimental diets for 12 d under conditions which excluded ultraviolet light. 3. Broiler chicks fed on diets with the higher concentration of cholecalciferol had higher Vmax and Km of the mucosa phytase, weight gain, feed intake, feed efficiency and percentage tibia ash, higher ileal digestibility of dry matter, energy, phosphorus (P) and calcium (Ca), and increased retention of dry matter, nitrogen, P, Ca and energy. 4. Broiler chicks receiving diets with the higher P concentration showed lower Vmax and Km of the intestinal mucosa phytase but greater weight gain, feed intake, feed efficiency and percentage tibia ash, higher ileal digestibility of dry matter, energy, P and nitrogen, and increased retention of dry matter, energy, nitrogen and Ca. 5. In conclusion, both dietary P and cholecalciferol influenced the activity of intestinal mucosa phytase.

6-Phytase↗

Excessive cholecalciferol in a layers diet: decline in some aspects of reproductive performance and increased bone mineralisation of progeny.

Feeding hens a diet containing 5,000 micrograms (200,000 ICU)/kg of cholecalciferol for four 28-d periods had no adverse effect on hen-day egg production or hatchability. Egg weight, shell quality, food consumption and fertility were significantly decreased in hens fed 5,000 micrograms/kg. of cholecalciferol compared with those fed 24 micrograms (960 ICU) cholecalciferol/kg diet. Plasma calcium increased significantly as the concentration of cholecalciferol was increased in the diet. However, no histologically detectable changes in the viscera or changes in the proportion of bone ash were observed with any concentration of the vitamin. Chicks hatched from dams receiving excessive doses of cholecalciferol (5,000 micrograms/kg) and maintained on a rachitogenic diet for 4 weeks had a significantly higher proportion of tibial ash but there was no effect on either body weight or tibial calcium.

Animals↗

Moderate excess of dietary vitamin E does not exacerbate cholecalciferol deficiency in young broiler chicks.

1. The combined effect of moderate excess dietary vitamin E and marginal amounts of dietary cholecalciferol on the performance and tibia bone ash of young male broiler chicks was evaluated. Vitamin E (alpha-tocopheryl acetate) and cholecalciferol were added to a commercial diet not already supplemented with these vitamins, at concentrations of 0 and 150 mg/kg, and 1.875, 5 and 25 micrograms/kg, respectively, and fed to chicks for 23 d. 2. Vitamin E concentration and its combinations with cholecalciferol did not significantly (P > 0.05) affect food intake, weight gain, food efficiency and bone ash. These variables were significantly (P < 0.001) lower in chicks fed on the diets supplemented with 1.875 micrograms cholecalciferol/kg compared with the values observed with the 2 other concentrations of this vitamin. There were no differences in the effects of 5 and 25 micrograms cholecalciferol/kg diet on the above variables. 3. It was concluded that vitamin E, at a concentration of 150 mg/kg diet, did not aggravate a mild cholecalciferol deficiency.

Animals↗

Relationship of mineral metabolism and long-term calcium and cholecalciferol supplementation to blood pressure in normotensive men.

To better understand the effects of calcium and cholecalciferol supplementation on blood pressure, we examined systolic and diastolic blood pressures in 65 men treated with 1000 mg Ca/d and 1000 IU cholecalciferol/d or placebo for 3 y. Subjects were normotensive and had no medical condition and took no medication known to affect mineral metabolism or blood pressure. At baseline, systolic blood pressure was positively related to fasting calcium excretion and negatively to ionized calcium concentrations. Phosphorus concentrations (negatively) and fasting calcium excretion (positively) were correlated with diastolic pressures. Nevertheless, calcium and cholecalciferol supplementation did not influence blood pressure at any time during the study. These results suggest that whereas calcium metabolism may be related to the control of blood pressure, dietary calcium and cholecalciferol intakes do not play a major role in its regulation in normotensive individuals. Calcium and cholecalciferol supplements should not be expected to have an effect on blood pressure in normotensive populations.

Adult↗

Effect to cholecalciferol and 1,25-Dihydroxycholecalciferol on the intestinal absorption of zinc in the chick.

The effect of cholecalciferol on the intestinal absorption of 65Zn was assessed in zinc-deficient and zinc-replete rachitic chicks, using the in situ ligated loop techniques. Cholecalciferol did not significantly affect 65Zn absorption in either group, although the synthesis of the intestinal calcium-binding protein (CaBP) in both groups was similar. In an analogous study, 1,25-dihydroxycholecalciferol increased 47Ca absorption and induced the synthesis of CaBP but exerted on effect on 65Zn absorption in zinc-deficient rachitic chicks. When fed a diet adequate in cholecalciferol, more CaBP was present in the intestine of the zinc-adequate group than in the zinc-deficient group, possibly due to the greater rate of growth and therefore the greater need for calcium by the former group. These results suggest that cholecalciferol and its most active metabolite do not directly affect zinc absorption and, by inference, that the vitamin D-dependent transport mechanism is not involved in zinc homeostasis, or in the interaction between calcium and zinc.

Animals↗

Metabolism of orally administered [3H]ergocalciferol and [3H]cholecalciferol by dairy calves.

Concentrations of ergocalciferol, cholecalciferol, and their metabolites in plasma were determined after a single oral dose of [3H]ergocalciferol or [3H]cholecalciferol was given to 95- to 105-kg Jersey bull calves. One group (three calves) was given 365 muCi of [3H]ergocalciferol (1.2 Ci/mmol) per calf, and the other group (three calves) was given 365 muCi of [3H]cholecalciferol (1.2 Ci/mmol) per calf. Fourteen blood samples were taken from each calf during the 3 weeks after administration. Total plasma radioactivity was highest at 80 hours in both groups (8400 dpm/ml and 4600 dpm/ml in the [3H]cholecalciferol- and [3H]ergocalciferol-treated calves, respectively). For determination of the time-dependent appearance and disappearance of plasma vitamin D and vitamin D metabolites, the plasma 3H-labeled steroids were extracted and separated by high-performance liquid chromatography. In both groups, [3H]vitamin D peaked at 24-48 hours and was the predominant radioactive form in plasma 10-15 hours after dosing. After 15 hours, 25-[3H]hydroxyvitamin D became the predominant labeled metabolite, reaching its maximal concentration between 48 and 96 hours. Concentrations of 25-[3H]hydroxycholecalciferol were about twice those of 25-[3H]hydroxyergocalciferol. The appearance/disappearance profile of 25,26-[3H]dihydroxycholecalciferol and 1,25[3H]hydroxycholecalciferol resembled that of 25-[3H]hydroxycholecalciferol.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Gastrointestinal absorption of lead in chicks: involvement of the cholecalciferol endocrine system.

The role of dietary calcium and phosphorus in modifying the intestinal absorption of lead and also the effect of lead ingestion on the metabolism of cholecalciferol were studied in chicks. The efficiency of absorption of 203Pb and 47Ca was increased when the animals were fed a low calcium diet and treated with cholecalciferol. The synthesis of the vitamin D-induced calcium-binding protein (CaBP) was correspondingly increased. When the chicks were depleted of vitamin D and repleted with 1,25-dihydroxycholecalciferol [1,25(OH)2D3] as their only source of the vitamin, the absorption of both 47Ca and 203Pb was unaffected by dietary calcium levels, and no change in CaBP levels occurred. Low dietary intake of phosphorus resulted in an increase in 47Ca and 203Pb absorption and in CaBP synthesis when the animals were treated with cholecalciferol. However, when the birds were repleted with 1,25(OH)2D3, the intestinal absorption of 47Ca and of 203Pb was increased, as well as the intestinal CaBP levels. Intracardial injection of increasing doses of 1,25(OH)2D3 to rachitic chicks resulted in a concomitant increase in 203Pb absorption in a manner that correlated with the degree of synthesis of CaBP. Ingestion of lead by the chicks was found to impair growth and renal production of 1,25(OH)2D3, resulting in lowered circulating and intestinal content of the hydroxylated metabolites of cholecalciferol.

Animals↗

Effect of treatment with cholecalciferol on the membrane potential and contractility of aortae from spontaneously hypertensive rats.

1. The diet of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NWR) was supplemented with 12.5 micrograms cholecalciferol per 100 g body weight daily, by gavage, for 4 weeks. 2. The amplitude of the contractile responses of aortic rings from SHR to potassium and adrenaline, which was smaller than in NWR aortae, was increased after treatment with cholecalciferol. No further changes were observed in the responses of NWR and SHR aortae in the presence of 100 nM apamin. 3. The membrane potentials of aortae from SHR, which were higher than those of aortae from NWR, decreased after treatment with cholecalciferol. Further depolarization was observed in aortic rings from NWR, but not in aortic rings from SHR, after their preincubation with 100 nM apamin. 4. It is concluded that cholecalciferol normalizes the membrane potential and contractility of aortae from SHR, probably through an effect on lipid composition and structure of the plasma membrane.

Animals↗

Absorption of silicon and aluminum by hens fed sodium zeolite A with various levels of dietary cholecalciferol.

Two experiments were conducted to determine whether 1) serum Si and Al is increased in hens intubated with sodium zeolite A (SZA); and 2) dietary cholecalciferol (vitamin D3) influences the absorption of Si or Al by hens fed SZA. In Experiment 1, hens were intubated at oviposition with 0, 1, or 2 g of SZA. Blood samples were collected from the brachial vein at oviposition, and 4, 8, 12, 16, and 20 h postoviposition. Serum samples were analyzed for Si and Al. Peak serum Si and Al were observed at 4 and 8 h postoviposition, respectively. In Experiment 2, hens consumed commercial layer diets ad libitum containing five levels of dietary cholecalciferol (100 to 500 IU/kg) with or without .75% SZA for 6 wk. Blood samples were collected at the end of the 6-wk period by cardiac puncture at oviposition. When dietary cholecalciferol was increased from 100 to 200 IU/kg of diet there was an increase (P < .05) in serum Si but not Al. Levels of cholecalciferol above 200 IU/kg did not produce an additional increase in serum Si. The results showed increased (P < .01) serum concentrations of Si and Al for hens intubated with or fed SZA. It was concluded that Si and Al from SZA are absorbed by commercial Leghorn hens, and a possible involvement of Si or Al should be considered in the mechanism of action of SZA associated with improved eggshell quality and bone development.

Absorption↗