DIFFERENTIAL TIME COURSE OF INDUCTION OF 1α,25-DIHYDROXYVITAMIN D3-24-HYDROXYLASE mRNA EXPRESSION IN RATS BY 1α,25-DIHYDROXYVITAMIN D3 AND ITS ANALOGS

Furuichi, Tatsuya; Kawata, Setsu; Asoh, Yoshinori; Kumaki, Kenji; Ohyama, Yoshihiko

doi:10.1016/s0024-3205(97)01139-9

Cited by 27 publications

(10 citation statements)

References 18 publications

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“…But the mRNA effect appeared transient, with near complete reversal by 24 hrs. This biphasic response of CYP24A1 to 1α,25(OH) 2 D 3 is similar what has been described in vivo in animals receiving repeated 1α,25(OH) 2 D 3 treatments [39, 40]. Although we were not able to measure 24R-hydroxylase activity in the LS180 cells, it could have had some importance during the 12–24 hr dose interval.…”

Section: Discussionsupporting

confidence: 86%

Human PXR-mediated induction of intestinal CYP3A4 attenuates 1α,25-dihydroxyvitamin D3 function in human colon adenocarcinoma LS180 cells

Zheng

Wang

Liao

et al. 2012

Biochemical Pharmacology

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Oxidative catabolism of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is mediated by either CYP24A1 or CYP3A4. In this paper, we tested whether induction of CYP3A4 in the LS180 intestinal cell model enhances clearance of 1α,25(OH)2D3 and blunts its hormonal effect on expression of the apical membrane calcium transport protein, TRPV6. Treatment with the hPXR agonist rifampin significantly increased CYP3A4 mRNA content and catalytic activity, but had no effect on CYP24A1 or TRPV6 mRNA content. Pre-treating cells with rifampin for 48 hrs, prior to a 24 hr 1α,25(OH)2D3 treatment phase, was associated with a subsequent 48% increase in the elimination of 1α,25(OH)2D3 and a 35% reduction of peak TRPV6 mRNA. Introduction of the CYP3A4 inhibitor, 6′,7′-dihydroxybergamottin, an active inhibitor in grapefruit juice, reversed the effects of rifampin on 1α,25(OH)2D3 clearance and TRPV6 expression. Over-expression of hPXR in LS180 cells greatly enhanced the CYP3A4 responsiveness to rifampin pretreatment, and elicited a greater relative suppression of TRPV6 expression and an increase in 1α,25(OH)2D3 disappearance rate, compared to vector expressed cells, following hormone administration. Together, these results suggest that induction of CYP3A4 in the intestinal epithelium by hPXR agonists can result in a greater metabolic clearance of 1α,25(OH)2D3 and reduced effects of the hormone on the intestinal calcium absorption, which may contribute to an increased risk of drug-induced osteomalacia/osteoporosis in patients receiving chronic therapy with potent hPXR agonists. Moreover, ingestion of grapefruit juice in the at-risk patients could potentially prevent this adverse drug effect.

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Section: Discussionsupporting

confidence: 86%

Human PXR-mediated induction of intestinal CYP3A4 attenuates 1α,25-dihydroxyvitamin D3 function in human colon adenocarcinoma LS180 cells

Zheng

Wang

Liao

et al. 2012

Biochemical Pharmacology

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“…After the injection, the low affinity of OCT to D-binding protein allows it to circulate primarily as the unbound form, and therefore promotes rapid clearance and facilitates its accessibility to target tissues [47]. The OCT was only 1/100 as active as 1,25(OH) 2 D 3 in inducing hypercalcemia [46]. This study showed no difference in serum calcium level among all experimental groups.…”

Section: Discussionmentioning

confidence: 89%

“…On the other hand, OCT, a vitamin D analog, overcomes these problems due to its lower calcemic effect and has a promising potential for clinical use. The biological effect of OCT is different from that of 1,25(OH) 2 D 3 , including different binding activity of OCT to vitamin D receptors and vitamin D-binding protein [46]. It has been estimated that the affinity of OCT to DBP is approximately 1/600 that of 1,25(OH) 2 D 3 [47].…”

Section: Discussionmentioning

confidence: 99%

Effects of 22-Oxa-Calcitriol on Podocyte Injury in Adriamycin-Induced Nephrosis

et al. 2011

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Background: In various animal studies, vitamin D has been shown to have a significant effect on reduction of proteinuria and the progression of kidney disease. However, little is known on its renoprotective effect in adriamycin (ADR)-induced nephrosis mice. The present study was intended to determine the therapeutic benefit of 22-oxa-calcitriol (OCT), a vitamin D analog, in reducing proteinuria and its renoprotective effect, i.e. preventing podocyte injury on ADR-induced nephrosis mice. Methods: Three experimental groups were used as follows: (1) nephrosis mice, established by a single intravenous injection of ADR; (2) ADR+OCT mice, nephrosis mice treated with OCT, and (3) mice treated only with OCT as the control group. Podocyte injury was assessed by podocyte apoptosis using the TUNEL assay, podocyte counting, podocyte-specific expressed protein by immunofluorescence and Western blot analysis, and foot process effacement using electron microscopy. Results: Lower proteinuria was observed in ADR+OCT mice. Improvement in glomerulosclerosis and interstitial fibrosis, and prevention of glomerular hyperfiltration were observed in ADR+OCT mice. Immunofluorescence and Western blot analyses showed restoration of downregulated expression of nephrin, CD2AP and podocin. Nevertheless, dendrin expression was not restored. An insignificant reduction in podocyte numbers was found in ADR+OCT mice. Complete foot process effacement was partially prevented in ADR+OCT mice. Conclusions: The results indicate that OCT reduces podocyte injury and has renoprotective effects in ADR nephrosis mice.

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“…However, OCT was only 1/100 as active as 1,25(OH) 2 D 3 in inducing hypercalcemia. 27 The precise mechanism of low activity of hypercalcemia is still unknown, however all published data showed rapid metabolic clearance caused by low affinity with binding proteins and low intestinal absorption through calciumbinding proteins.…”

Section: Discussionmentioning

confidence: 99%

A Vitamin D Analog Ameliorates Glomerular Injury on Rat Glomerulonephritis

Makibayashi

Tatematsu

Hirata³

et al. 2001

The American Journal of Pathology

122

106

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OCT (22-oxa-calcitriol), a vitamin D analog, has been reported to show strong inhibitory effects on mesangial cell proliferation in vitro.In the present study, we report a study of the effect of OCT on anti-thy-1 glomerulonephritis. Both OCT and 1,25(OH) 2 D 3 significantly inhibited mesangial cell proliferation, the degree of glomerulosclerosis, and albuminuria at day 8 compared to the disease control group. The OCTtreated group showed normal calcium levels but the 1,25(OH) 2 D 3 -treated group showed higher levels. The disease control group showed a marked increase of type I and type IV collagens, and ␣-smooth muscle actin (␣-SMA) compared to the normal group. The treatment of OCT or 1,25(OH) 2 D 3 significantly reduced the expression of these proteins. The mRNA of the glomeruli of anti-thy-1 model expressed significantly higher levels of type I and type IV collagens, and ␣-SMA at day 8 compared to normal rats. Treatment with OCT or 1,25(OH) 2 D 3 inhibited the mRNA expressions of type I and type IV collagens, as well as that of ␣-SMA. These data demonstrate that OCT inhibits mesangial cell proliferation and extracellular matrix expansion with a low calcemic activity. Disease control rats showed significantly increased levels of transforming growth factor-␤1 protein in the glomeruli, but treatment with OCT or 1,25(OH) 2 D 3 markedly reduced this expression. The levels of mRNA in glomeruli were also consistent with these protein levels. Therefore, the suppressive effect of OCT may be mediated by inhibition of transforming growth factor-␤1. The present results suggest that OCT has potential for use in therapeutic strategy for the treatment of glomerulonephritis without inducing hypercalcemia. (Am J Pathol 2001, 158:1733-1741) A number of progressive glomerular diseases are characterized by initial mesangial cell proliferation, which is followed by glomerulosclerosis, and finally develops to end-stage kidney disease. Examples of this process are membranoproliferative glomerulonephritis, diabetic nephropathy, and IgA nephropathy.1,2 Nonanticoagulant heparin, a potent in vitro inhibitor of mesangial cell proliferation, inhibits mesangial cell proliferation and matrix expansion in mesangioproliferative glomerulonephritis. 3Treatment with anti-platelet-derived growth factor also blocks mesangial cell proliferation in vivo, preventing the development of glomerulosclerosis. 4 This suggests that mesangial cell proliferation may play an important role in the development of glomerular lesions. Therefore, the search for agents capable of inhibiting mesangial cell proliferation is clinically important for progressive glomerular change.Recently, 1,25(OH) 2 D 3 was shown to have a preventive effect in progressive glomerular damage in a renal ablation model. 5 However, 1,25(OH) 2 D 3 has an adverse effect in that its use leads to hypercalcemia and hyperphosphatemia, which eventually represent risk factors for the progression of renal injury. It is, therefore, difficult to use 1,25(OH) 2 D 3 for the practical treatment of patie...

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DIFFERENTIAL TIME COURSE OF INDUCTION OF 1α,25-DIHYDROXYVITAMIN D3-24-HYDROXYLASE mRNA EXPRESSION IN RATS BY 1α,25-DIHYDROXYVITAMIN D3 AND ITS ANALOGS

Cited by 27 publications

References 18 publications

Human PXR-mediated induction of intestinal CYP3A4 attenuates 1α,25-dihydroxyvitamin D3 function in human colon adenocarcinoma LS180 cells

Human PXR-mediated induction of intestinal CYP3A4 attenuates 1α,25-dihydroxyvitamin D3 function in human colon adenocarcinoma LS180 cells

Effects of 22-Oxa-Calcitriol on Podocyte Injury in Adriamycin-Induced Nephrosis

A Vitamin D Analog Ameliorates Glomerular Injury on Rat Glomerulonephritis

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