Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats

From studies on different species and in cell culture systems, it has been suggested that vitamin D metabolites might affect themetabolism and elimination of xenobiotics. Although most studies performed on rodents and cell cultures report an upregulationof respective enzymes and transporters, data from the literature are inconsistent. Especially results obtained with sheep differ fromthese observations. As vitamin D metabolites are widely used as feed additives or therapeutics in livestock animals, we aimed toassess whether these differences indicate species-specific responses or occurred due to the very high dosages used in the rodentstudies. -erefore, we applied treatment protocols to rats that had been used previously in sheep or cattle. Forty-eight female ratswere divided into three treatment and corresponding placebo groups: (1) a single intraperitoneal injection of 1,25-(OH)2D3 orplacebo 12 h before sacrifice; (2) daily supplementation with 25-OHD3 by oral gavage or placebo for 10 days; and (3) a singleintramuscular injection of vitamin D3 10 days before sacrifice. In contrast to a previous study using sheep, treatment of rats with1,25-dihydroxyvitamin D3 did not result in an upregulation of cytochrome P450 3A isoenzymes (CYP3A), but a decrease wasfound in hepatic and intestinal expressions. In addition, a downregulation of P-glycoprotein (P-gp) and breast cancer resistanceprotein was found in the brain. Taken together, the stimulating effects of vitamin D metabolites on the expression of genesinvolved in the metabolism and elimination of xenobiotics reported previously for rodents and sheep could not be reproduced. Incontrast, we even observed a negative impact on the expression of CYP3A enzymes and their most important regulator, thepregnane X receptor. Most interestingly, we could demonstrate an effect of treatment with 25-hydroxyvitamin D3 and vitamin D3on the functional activity of ileal P-glycoprotein (P-gp) using the Ussing chamber technique.Fil: Klumpp, Karoline. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Lange, Frauke. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Muscher-Banse, Alexandra S.. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Schnepel, Nadine. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Hansen, Kathrin. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Maté, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Wilkens, Mirja. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemani

Comparative Study of the Effects of Two Dietary Sources of Vitamin D on the Bone Metabolism,Welfare and Birth Progress of Sows Fed Protein- and Phosphorus-Reduced Diets

To investigate the influence of two dietary sources of vitamin D on the vitamin D status, bone metabolism, welfare and birth progress of gestating and lactating sows, forty-nine multiparous sows were randomly assigned to one of two diets: “CON” (n = 25; 50 g vitamin D3/kg feed) and “HYD” (n = 24; 50 g 25-hydroxycholecalciferol/kg feed). The basal diets were protein- and phosphorus-reduced. The trial started on day 3 ante insemination of the sows and ended with weaning of the piglets on day 28 postpartum. Dietary supplementation of 25-hydroxycholecalciferol resulted in improved maternal vitamin D status (p < 0.001), fewer gait changes (p < 0.01) and longer standing time after feeding (day 5 ante partum; p < 0.05) compared to vitamin D3. However, the bone markers CrossLaps and osteocalcin were not affected. Overall, the present results suggest that sows fed 25-hydroxycholecalciferol instead of vitamin D3 showed improved locomotion and stance strength. However, this outcome is probably not related to altered bone metabolism. The underlying mechanisms must be investigated in further studies

Comparative Study of the Effects of Two Dietary Sources of Vitamin D on the Bone Metabolism,Welfare and Birth Progress of Sows Fed Protein- and Phosphorus-Reduced Diets

To investigate the influence of two dietary sources of vitamin D on the vitamin D status, bone metabolism, welfare and birth progress of gestating and lactating sows, forty-nine multiparous sows were randomly assigned to one of two diets: “CON” (n = 25; 50 g vitamin D3/kg feed) and “HYD” (n = 24; 50 g 25-hydroxycholecalciferol/kg feed). The basal diets were protein- and phosphorus-reduced. The trial started on day 3 ante insemination of the sows and ended with weaning of the piglets on day 28 postpartum. Dietary supplementation of 25-hydroxycholecalciferol resulted in improved maternal vitamin D status (p < 0.001), fewer gait changes (p < 0.01) and longer standing time after feeding (day 5 ante partum; p < 0.05) compared to vitamin D3. However, the bone markers CrossLaps and osteocalcin were not affected. Overall, the present results suggest that sows fed 25-hydroxycholecalciferol instead of vitamin D3 showed improved locomotion and stance strength. However, this outcome is probably not related to altered bone metabolism. The underlying mechanisms must be investigated in further studies

Differences in peripartal plasma parameters related to calcium homeostasis of dairy sheep and goats in comparison with cows

Recently it has been demonstrated that there are differences between sheep and goats in respect to adaptation to a calcium-restricted diet. It was the aim of the present study to evaluate whether species-specific peculiarities also occur when calcium homoeostasis is challenged by lactation. Therefore, we investigated the time courses of plasma parameters related to calcium homoeostasis (calcium, phosphate, calcitriol, the bone resorption marker CrossLaps® and the bone formation marker osteocalcin) during the transition period in multiparous animals of both species and compared the results to data from a former study carried out with dairy cows. As in cows, plasma calcium and the ratio of bone formation to bone resorption decreased at parturition in goats while plasma calcitriol increased. On day 10 post partum the bone parameters of goats reached prepartum values again, which was not the case in cows. Sheep were found to experience a challenge of calcium homoeostasis already 10d before parturition, reflected by a very low ratio of bone formation to bone resorption, which was not accompanied by an increase in plasma calcitriol. Additionally, sheep and goats which had been in milk for 3 months were sampled, dried-off and sampled again 6 weeks later. In dried-off animals there were no detectable differences in parameters of bone metabolism. In conclusion we could show that the contribution of bone mobilisation to the compensation for the enhanced calcium demand due to lactation differs between the three ruminant specie

Calcinosis in Alpaca Crias (Vicugna pacos) Due to Vitamin D Intoxication—Clinical, Laboratory and Pathological Findings with a Focus on Kidney Function

Alpacas kept in Central Europe are often deficient in vitamin D3, which is supplemented orally or by injection by the owners or veterinarians. Vitamin D3 can be specified in two different units (IU and µg), which differ by a factor of 40. By mixing up these units, an overdosage can be induced. In this study, three alpaca crias were examined after vitamin D3 intoxication, with particular reference to kidney function. All three animals developed non-specific clinical alterations 1–2 weeks after a vitamin D3 overdose of approximately 40 times. Plasma of the animals revealed several alterations. The main findings were severe azotemia, hypercalcemia and hyperphosphatemia, 15 days after treatment. Kidney function analysis (endogenous creatinine clearance) in two of the crias revealed severe glomerular damage. All crias died despite intensive treatment within 23 days after vitamin D3 treatment. Necropsy revealed calcification in different organs, mainly the kidneys, lungs and liver. Since nine other crias in the same group were treated with comparable doses of vitamin D3 and no clinical signs were observed in these animals, it is concluded that individual animals show different levels of sensitivity to vitamin D3