Hepatic metabolism of vitamin D3 in streptozotocin-induced diabetic rat

1980 ◽  
Vol 93 (3) ◽  
pp. 346-350 ◽  
Author(s):  
Sorel Sulimovici ◽  
Martin S. Roginsky
Keyword(s):  
Vitamin D ◽  
Liver Microsomes ◽  
Hepatic Metabolism ◽  
Enzymic Activity ◽  
Diabetic Rat ◽  
Hydroxyvitamin D ◽  
Streptozotocin Induced Diabetes ◽  
25 Hydroxyvitamin D ◽  
Isolated Liver

Abstract. The effect of streptozotocin-induced diabetes on the in vitro conversion of vitamin D3 to 25-hydroxyvitamin D3 (25-OHD3) by isolated liver microsomes from rachitic rats was examined. Enzymic activity was significantly less than that observed in control animals (P< 0.001). Administration of insulin restored activity almost to control values. These findings provide evidence that diabetes in this animal model produces alterations in the metabolism of vitamin D.

scholarly journals Therapeutic Effects of 25-Hydroxyvitamin D on the Pathological Process of Benign Prostatic Hyperplasia: An In Vitro Evidence

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yanbo Chen ◽  
Hui Xu ◽  
Chong Liu ◽  
Meng Gu ◽  
Qi Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Benign Prostatic Hyperplasia ◽  
Prostatic Hyperplasia ◽  
Therapeutic Effects ◽  
Prostate Cell ◽  
Mesenchymal Transition ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

The pathogenesis of benign prostatic hyperplasia (BPH) is extremely complicated which involving the multiple signaling pathways. The deficiency of vitamin D is an important risk factor for BPH, and exogenous vitamin D is effective for the treatment of BPH. In this study, we provided in vitro mechanical evidence of vitamin D as a treatment for BPH using BPH-1, WPMY-1, and PBMC cells. We found that 25-hydroxyvitamin D (25-OH D) level is decreased in BPH and closely correlated with age, prostate volume, maximum flow, international prostate symptom score, and prostate-specific antigen of the BPH patients. We further revealed that 25-OH D ameliorated TGF-β1 induces epithelial-mesenchymal transition (EMT) of BPH-1 cells and proliferation of WPMY-1 cells via blocking TGF-β signaling. Moreover, 25-OH D was able to block NF-κB signaling in PBMCs of BPH patients and STAT3 signaling in BPH cells to relieve inflammation. 25-OH D also protects BPH cells from inflammatory cytokines selected by PBMCs. Finally, we uncovered that 25-OH D alleviated prostate cell oxidative stress by triggering Nrf2 signaling. In conclusion, our data verified that 25-OH D regulated multiple singling pathways to restrain prostate cell EMT, proliferation, inflammation, and oxidative stress. Our study provides in vitro mechanical evidence to support clinical use of vitamin D as a treatment for BPH.

Low Vitamin D Levels Are Associated with Inferior Survival Following Azacitidine Treatment in Patients with Myelodysplastic Syndrome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1699-1699
Author(s):  
Aleksandar Radujkovic ◽  
Paul Schnitzler ◽  
Anthony D. Ho ◽  
Peter Dreger ◽  
Thomas Luft
Keyword(s):  
Vitamin D ◽  
Overall Survival ◽  
Bone Homeostasis ◽  
Serum Samples ◽  
Antiproliferative Effects ◽  
Hydroxyvitamin D ◽  
Vitamin D Levels ◽  
25 Hydroxyvitamin D

Abstract Introduction: Azacitidine (AZA) therapy has become the recommended first-line treatment for patients with high-risk myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML; bone marrow blasts <30%). However, only around 50% of patients achieve objective responses with AZA therapy and the vast majority of responding patients have disease progression within 2 years resulting in dismal survival rates. Vitamin D (VitD) is a central regulator of calcium and bone homeostasis and affects multiple signaling pathways controlling proliferation, apoptosis and differentiation. More than 30 years ago, VitD was demonstrated to induce in vitro differentiation of AML blast cells. Consequently, VitD alone or in combination with other differentiating agents has been used for treatment of MDS patients showing inconsistent and rather limited efficacy. We retrospectively tested the hypothesis that VitD levels prior to start of treatment are predictive of overall survival (OS) in newly diagnosed MDS and oligoblastic AML patients receiving upfront AZA therapy. In addition, the antiproliferative effects of AZA in combination with different VitD derivatives were investigated in vitro. Patients, materials and methods: A total of 58 patients treated at our center between 2006 and 2014 had serum samples available for assessment of VitD status. Serum samples were collected at a median of 18 days prior to start of AZA treatment and cryopreserved at -80°C. VitD status was assessed by measurement of circulating 25-hydroxyvitamin D levels applying a standard chemiluminescent immunoassay (DiaSorin Deutschland GmbH, Dietzenbach, Germany). Overall survival (OS) was estimated using the method of Kaplan and Meier. Survival times were measured from the date of AZA treatment start. Comparison of OS between the VitD groups was done using the logrank test and by cox regression adjusting for known confounders. For in vitro analyses, a tetrazolium based MTT assay was used for assessment of growth inhibition of two different AML cell lines (HL60 and MOLM13) after exposure to AZA alone or in combination with VitD (1alpha,25-dihydroxyvitamin D and 25-hydroxyvitamin D; both from Cayman Chemical, Ann Arbor, MI, USA) or the VitD antagonist TEI-9647 (kindly provided by Teijin Pharma Ltd., Tokyo, Japan). Drug interactions were analyzed using the median-effect method of Chou and Talalay and combination index (CI) values were calculated according to the classic isobologramm equation with CI<1, CI=1 or CI>1 corresponding to synergism, additivity or antagonism, respectively. In cases where no antiproliferative activity upon single-agent treatment was assessable (low-dose VitD and TEI-9647), an analysis in terms of sensitization (potentiation) or inhibition of AZA activity was performed instead. Results: Estimated median follow-up time was 14.2 months. Median serum VitD level prior to AZA treatment was 33 nM (range 11-102 nM). A total of 18 patients underwent allogeneic stem cell transplantation (alloSCT) following AZA therapy and follow-up was censored at the time of alloSCT. Patient, disease and treatment characteristics did not differ significantly between the low (≤33 nM; n=29) and high (>33 nM; n=29) VitD group. Estimated one-year survival was 72% (95% CI 54-90%) in the high VitD group, which was significantly longer as compared to the low VitD group (41%, 95% CI 20-62%, p<0.05; Figure 1). In multivariate analysis with OS as endpoint, VitD (per 10 nM decrease, HR 1.83 95% CI 1.06-3.16, p=0.03) and adverse cytogenetics (HR 2.58 95% CI 1.10-6.06, p=0.03) were independent predictors of shorter survival. In vitro treatment of HL60 and MOLM13 cells with AZA in combination with VitD produced synergistic and additive antiproliferative effects. Addition of nanomolar concentrations of VitD to AZA resulted in potentiation of AZA activity. Conversely, combination with TEI-9647 resulted in inhibition of AZA activity. Conclusions: Our study suggests that higher VitD levels were associated with a survival advantage following upfront AZA therapy. As compared to AZA monotherapy combination treatment with VitD resulted in enhanced cytotoxic effects in vitro. VitD repletion/supplementation during AZA treatment should therefore be explored. Disclosures Luft: Immundiagnostik AG: Research Funding.

Metabolism of 25-hydroxyvitamin D in copper-laden rat: a model of Wilson's disease

1988 ◽  
Vol 254 (2) ◽  
pp. E150-E154
Author(s):  
T. O. Carpenter ◽  
M. L. Pendrak ◽  
C. S. Anast
Keyword(s):  
Vitamin D ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Hepatic Copper ◽  
25 Hydroxyvitamin D ◽  
Potential Factor

Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. We investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D3 [25(OH)D3] resulted in reduced 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in copper-intoxicated rats. In vitro 25(OH)D-1 alpha-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondria from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH)2D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease.

Effects of streptozotocin-induced diabetes on circulating levels of vitamin D metabolites

1983 ◽  
Vol 104 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Hitoshi Ishida ◽  
Yutaka Seino ◽  
Kinsuke Tsuda ◽  
Jiro Takemura ◽  
Sigeo Nishi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Diabetic Rats ◽  
Plasma Vitamin ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Plasma Urea ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Streptozotocin Induced Diabetes ◽  
25 Hydroxyvitamin D

Abstract. In order to investigate vitamin D metabolism in insulin-deficient diabetic rats, plasma vitamin D metabolites were measured at various periods after induction of diabetes by iv administration of 60 mg/kg streptozotocin (STZ). After STZ injection, plasma insulin was significantly decreased and plasma urea nitrogen increased with the duration of diabetes, while plasma creatinine remained unchanged. Plasma calcium, 25-hydroxyvitamin D (25(OH)D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) progressively decreased. On the other hand, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) did not change at any period, but the ratio of 1,25(OH)2D to 25(OH)D became high in proportion to the severity of hypocalcaemia. Since significantly lower 25(OH)D and 24,25(OH)2D levels were observed at the later stage of diabetes, it is suggested that the altered vitamin D metabolism in diabetes is secondary to the disturbances in metabolic homeostasis derived form the insulin deficiency.

Effect of magnesium depletion on metabolism of 25-hydroxyvitamin D in rats

1987 ◽  
Vol 253 (1) ◽  
pp. E106-E113
Author(s):  
T. O. Carpenter ◽  
D. L. Carnes ◽  
C. S. Anast
Keyword(s):  
Vitamin D ◽  
Animal Studies ◽  
Magnesium Deficiency ◽  
Hydroxylase Activity ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Magnesium Depletion ◽  
25 Hydroxyvitamin D

Resistance to vitamin D in magnesium depletion has been observed in humans and in animal studies. Variable levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] have been reported in patients with magnesium depletion, and studies of vitamin D metabolism in states of magnesium depletion have not yielded consistent results. We examined effects of magnesium deprivation on circulating 1,25(OH)2D levels before and after a loading dose of 25-hydroxyvitamin D3 [25(OH)D3], on in vivo conversion of small doses of radiolabeled 25(OH)D3 to 1,25(OH)2D3 in intact rats, and on in vitro 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity in rat renal mitochondria. The effects of magnesium-free media on mitochondrial 1 alpha-hydroxylase activity was examined. Magnesium depletion did not affect in vivo conversion of 25(OH)D to 1,25(OH)2D. In vitro 1 alpha-hydroxylase activity was comparable in magnesium-replete and -deplete animals and was evident in the absence of added magnesium in incubation media. Our in vivo and in vitro studies are consistent with one another and demonstrate that in the rat conversion of 25(OH)D to 1,25(OH)2D is unimpaired in magnesium deficiency. Resistance to vitamin D in magnesium depletion is likely due to the impaired skeletal responsivity to 1,25(OH)2D, as demonstrated in earlier studies.

Effect of phenobarbital treatment on metabolism of vitamin D by rat liver

1983 ◽  
Vol 245 (1) ◽  
pp. E55-E59
Author(s):  
D. T. Baran
Keyword(s):  
Vitamin D ◽  
Rat Liver ◽  
Blood Levels ◽  
Perfusion System ◽  
Vitamin D Metabolism ◽  
Hepatic Perfusion ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

Phenobarbital has been postulated to impair hepatic conversion of vitamin D to 25-hydroxyvitamin D [25(OH)D] either by accelerating the conversion of vitamin D to biologically inactive products or by directly inhibiting 25(OH)D production. The effect of a dose of phenobarbital documented to decrease circulating 25(OH)D levels on hepatic vitamin D metabolism has been investigated in rachitic rats with a recycling in vitro hepatic perfusion system. Phenobarbital (75 mg/kg/day) administered intraperitoneally to D-replete rats increased circulating 25(OH)D blood levels after 4 wk of therapy but was attended by decreased levels after 6 and 8 wk. Rachitic rats were then injected daily with phenobarbital for either 4 or 8 wk and the livers removed and perfused at a rate of 15 ml/min for 3 h. The concentrations of [3H]25(OH)D in the hepatic perfusate at 3 h was decreased after both 4 and 8 wk of phenobarbital. Although total [3H]-25(OH)D production (hepatic plus perfusate) was unaffected by phenobarbital, the efficiency of hepatic production was decreased after 8 wk of treatment and the release of [3H]-25(OH)D from the liver into the perfusate was inhibited after both 4 and 8 wk. The data indicate that chronic phenobarbital therapy decreases both the release of [3H]25(OH)D from the liver into the perfusate and the efficiency of hepatic [3H]-25(OH)D production. Phenobarbital-induced inhibition of 25(OH)D release from the liver may be another mechanism for the low 25(OH)D levels noted in humans after long-term phenobarbital therapy.

Depressed Serum 25-Hydroxyvitamin D Levels Increase Hospital Stay and Alter Glucose Homeostasis in First-ever Ischemic Stroke

2019 ◽  
Vol 16 (4) ◽  
pp. 340-347
Author(s):  
Yuge Wang ◽  
Yanqiang Wang ◽  
Bingjun Zhang ◽  
Yinyao Lin ◽  
Sha Tan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Ischemic Stroke ◽  
Hospital Stay ◽  
Functional Outcome ◽  
Vitamin D Deficiency ◽  
Glucose Homeostasis ◽  
Clinical Severity ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Deficiency Group

Background and Objective: Vitamin D deficiency is internationally recognized among the potentially modifiable risk factors for ischemic cardio-cerebrovascular diseases. However, the association between vitamin D deficiency and stroke morbidity or mortality remains insufficiently known. Our aim is to investigate their relevance to 25-hydroxyvitamin D [25(OH) D] levels and clinical severity and outcome after 3 months in first-ever ischemic stroke. Methods: Retrospective analysis of 356 consecutive patients in first-ever ischemic stroke between 2013 and 2015. Serum 25(OH) D levels were measured at baseline. Stroke severity was assessed at admission using the National Institutes of Health Stroke Scale (NIHSS) score. Functional outcome after 3 months of onset was evaluated using the modified Rankin scale (mRS). Results: Among the 356 enrolled patients, HbA1c was higher in insufficiency/deficiency group than that in the sufficiency group (6.3 ± 1.7 vs. 5.9 ± 1.1, p =0.015). The hospital stay was longer in insufficiency/deficiency group than that in the sufficiency group (11 (8-17) vs. 9.5 (7-13), p = 0.035). There was a significant inversed trend between serum 25(OH) D levels and hospital stay (OR 0.960, P = 0.031), using logistic regression. Conclusions: 25(OH)D levels are associated with glucose homeostasis, 25(OH) D contributes to increase the length of hospital stay. Low serum 25-OHD level is an independent predictor for hospital stay in first-ever ischemic stroke. Vitamin D deficiency did not predict functional outcome in the span of 3 months.

scholarly journals Role of glucuronidated 25-hydroxyvitamin D on colon gene expression in mice

2020 ◽  
Vol 319 (2) ◽  
pp. G253-G260
Author(s):  
Carmen J. Reynolds ◽  
Nicholas J. Koszewski ◽  
Ronald L. Horst ◽  
Donald C. Beitz ◽  
Jesse P. Goff
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

We found that 25OHD-Gluc, an endogenously produced metabolite, is delivered to the colon via bile to induce vitamin D-mediated responses in the colon.

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