Reduced hepatic synthesis of calcidiol in uremia.

Calcidiol insufficiency is highly prevalent in chronic kidney disease (CKD), but the reasons for this are incompletely understood. CKD associates with a decrease in liver cytochrome P450 (CYP450) enzymes, and specific CYP450 isoforms mediate vitamin D(3) C-25-hydroxylation, which forms calcidiol. Abnormal levels of parathyroid hormone (PTH), which also modulates liver CYP450, could also contribute to the decrease in liver CYP450 associated with CKD.

Implication of caspases and subcellular compartments in tert-butylhydroperoxide induced apoptosis.

Oxidative stress has been implicated in many physiopathologies including neurodegenerative diseases, cancer, cardiovascular and respiratory diseases, and in mechanisms of action of environmental toxicants. tert-butylhydroperoxide (t-BHP) is an organic lipid hydroperoxide analogue, which is commonly used as a pro-oxidant for evaluating mechanisms involving oxidative stress in cells and tissues. This study investigates mechanisms of apoptosis induced by oxidative stress in hepatocytes, in particular, the involvement of caspases and subcellular compartments.

Endocrine and bone consequences of cyclic nutritional changes in the calcium, phosphate and vitamin D status in the rat: an in vivo depletion-repletion-redepletion study.

Hypocalcemia secondary to vitamin D3 (D3) depletion (D-Ca-) perturbs extra- and intracellular calcium (Ca). To study the effect of cyclic nutritional changes in the D3 and calcium (Ca) repletion state, we investigated the lasting effects of calcium or D3 repletion on calcium and bone metabolism using a novel depletion-repletion-redepletion protocol. D-Ca- rats presenting osteomalacia without rickets and a significant impairment in whole body mineral content (BMC) accretion were repleted with either calcium alone [3% (Ca+3) or 0.

The normal liver harbors the vitamin D nuclear receptor in nonparenchymal and biliary epithelial cells.

The liver is generally considered negative for the vitamin D nuclear receptor (VDR(n)), even though several studies have shown significant effects of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on liver cell physiology. The low abundance of VDR(n) in the liver led us to propose that hepatocytes (the largest hepatic cell population) were most likely negative for the receptor, whereas the small hepatic sinusoidal and ductular cell populations that contain cell types known to express VDR(n) in other tissues should express the receptor. Using freshly isolated cells from normal livers as well as biliary and epithelial hepatic cell lines, our data show that the human, rat, and mouse hepatocytes express very low VDR(n) messenger RNA (mRNA) and protein levels.

Calcitriol regulates the expression of the genes encoding the three key vitamin D3 hydroxylases and the drug-metabolizing enzyme CYP3A4 in the human fetal intestine.

Background And Aims: The human fetal jejunum has been shown to harbour the vitamin D3 (D3) nuclear receptor (VDRn) and to be responsive to calcitriol/1,25-dihydroxyvitamin D3[1,25(OH)2D3] through modulation of proliferation and differentiation processes. The aim of the study was to evaluate the presence as well as the effect of 1,25(OH)2D3 exposure on the expression levels of the three key D3-hydroxylase gene transcripts (25-hydroxylase, CYP27A; 24-hydroxylase, CYP24; 1alpha-hydroxylase, CYP27B1) as well as that of the 1,25(OH)2D3-responsive endobiotic/xenobiotic metabolizing enzyme CYP3A4 (which is also considered a major detoxifiying enzyme) in the human proximal and distal intestine.methods Specimens from normal fetuses ranging from 15 to 20 weeks of gestation were obtained following elective termination of normal pregnancies.

High sensitivity of rat hepatic vitamin D3-25 hydroxylase CYP27A to 1,25-dihydroxyvitamin D3 administration.

CYP27A is considered the main vitamin D(3) (D(3))-25 hydroxylase in humans. Our purpose was to evaluate the effect of the D(3) nutritional and hormonal status on hepatic CYP27A mRNA, cellular distribution, transcription rate, and enzyme activity. Studies were carried out in normal and in D-depleted rats supplemented with D(3), 25OHD(3), or 1,25(OH)(2)D(3).

Effect of cyclosporine a on hepatic compensatory growth: role of calcium status.

Cyclosporine A (CsA) has been reported to positively influence hepatic compensatory growth (HCG) in normal animals. The role of calcium in the CsA-mediated influence on HCG was studied in normal and in chronically hypocalcemic rats, a model in which HCG is perturbed. CsA (3.

Mechanism of tert-butylhydroperoxide induced apoptosis in rat hepatocytes: involvement of mitochondria and endoplasmic reticulum.

The purpose of the present work was to study the mechanisms involved in apoptosis induced by oxidative stress in rat hepatocytes. We focused on the apoptotic signaling molecules cytochrome c, Bcl-2 and Bax. Rat hepatocytes were exposed for 1 h to increasing concentrations of tert-butylhydroperoxide (t-BHP).

Downregulation of hepatic cytochrome P450 in chronic renal failure.

Chronic renal failure (CRF) is associated with a decrease in drug metabolism. The mechanism remains poorly understood. The present study investigated the repercussions of CRF on liver cytochrome P450 (CYP450).