Does vitamin D prevent radiotherapy-induced toxicity?

AbstractVitamin D is known as the bone hormone, it is also know that it has effects on cancer because of its anti-inflammatory and immunomodulatory characteristics and its effects on cytokine levels. It is seen that vitamin D use together with radiotherapy can have a positive effect on cancer treatment. It should be investigated whether toxicities due to radiation is prevented by vitamin D metabolites’ increasing the induction of immunomodulator cells and the capacities of immune response cells. Use of 1,25[OH]2 Vitamin D3 analogs as an adjuvant immunomodulator for patients receiving radiotherapy should be evaluated. There is a need for studies to be done in this regard.

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Pro- and Anti-Inflammatory Cytokines in the First Trimester—Comparison of Missed Miscarriage and Normal Pregnancy

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18168538 ◽

2021 ◽

Vol 18 (16) ◽

pp. 8538

Author(s):

Maciej Kwiatek ◽

Tomasz Gęca ◽

Anna Kwaśniewska

Keyword(s):

Immune Response ◽

Inflammatory Cytokines ◽

First Trimester ◽

Normal Pregnancy ◽

Control Group ◽

Study Group ◽

Tnf Α ◽

Cytokine Levels ◽

Anti Inflammatory ◽

Tgf Β1

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.

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Stimulation of 24R,25-dihydroxyvitamin D3 synthesis by metabolites of vitamin D3

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1983.245.4.e359 ◽

1983 ◽

Vol 245 (4) ◽

pp. E359-E364 ◽

Cited By ~ 1

Author(s):

G. S. Reddy ◽

G. Jones ◽

S. W. Kooh ◽

D. Fraser ◽

H. F. DeLuca

Keyword(s):

Vitamin D ◽

Vitamin D3 ◽

The Other ◽

Hydroxyl Group ◽

Vitamin D Metabolites ◽

Structural Requirements ◽

Dihydroxyvitamin D3 ◽

Hydroxylated Metabolites ◽

Perfusion Period ◽

Stimulation Of

Previously we have shown that the isolated perfused kidney from vitamin D-deficient rats converts [3H]25(OH)D3 into [3H]1 alpha,25(OH)2D3. When certain vitamin D metabolites were added to perfusate the same kidney began to synthesize [3H]24R,25(OH)2D3. In this study we investigated the structural requirements of the vitamin D molecule necessary to stimulate synthesis of [3H]24R,25(OH)2D3 in a 1-hydroxylating kidney. Kidneys were perfused with tracer [3H]25(OH)D3 (450 pM) alone and in the presence of a variety of hydroxylated metabolites and fluorinated analogues of vitamin D3 at concentrations of 450 pM to 25 microM. Tracer [3H]25(OH)D3 alone resulted in synthesis of only [3H]1 alpha,25(OH)2D3 during the 6-h perfusion period. 25-Hydroxylated metabolites [25(OH)D3, 25 nM; 1 alpha,25(OH)2D3, 25 nM; 24R,25(OH)2D3, 25 nM; 24(F)2,25(OH)D3, 50 nM] stimulated [3H]24R,25(OH)2D3 production at 2 h of perfusion. On the other hand, analogues without the 25-hydroxyl group [D3; 1 alpha(OH)D3; 25(F)D3; 1 alpha(OH),25(F)D3; 1 alpha(F)D3; 1 beta(F)D3]; did not stimulate [3H]24R,25(OH)2D3 synthesis. We conclude that the 25-hydroxyl group is an essential determinant of 24-hydroxylation.

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Determination of Vitamin D and Its Metabolites in Human Brain Using an Ultra-Pressure LC–Tandem Mass Spectra Method

Current Developments in Nutrition ◽

10.1093/cdn/nzz074 ◽

2019 ◽

Vol 3 (7) ◽

Cited By ~ 3

Author(s):

Xueyan Fu ◽

Gregory G Dolnikowski ◽

William B Patterson ◽

Bess Dawson-Hughes ◽

Tong Zheng ◽

...

Keyword(s):

Vitamin D ◽

Corpus Callosum ◽

Human Brain ◽

Vitamin D3 ◽

Temporal Cortex ◽

National Development ◽

Brain Regions ◽

Accurate Information ◽

Vitamin D Metabolites

ABSTRACTBackgroundLow serum total 25-hydroxyvitamin D3 [25(OH)D3] concentrations have been associated with cognitive impairment. However, it is unclear if serum 25(OH)D3 concentrations are a valid indicator of the concentrations of vitamin D and its metabolites in human brain.ObjectivesThe aim of this study was to develop and validate a method to quantify vitamin D3, 25(OH)D3, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in human brain.MethodsThe assay developments were performed using porcine brains. Liquid extraction was used in homogenized samples (∼0.1 g each) prior to analysis by LC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione. This method was then applied to the determination of vitamin D and its metabolites in a whole human brain obtained from the National Development and Research Institutes.ResultsThe method showed good linearity of vitamin D3, 25(OH)D3, and 1,25(OH)2D3 over the physiological range (R2 = 0.9995, 0.9968, and 0.9970, respectively). The lowest detection limit for vitamin D3, 25(OH)D3, and 1,25(OH)2D3 in porcine brain was 25, 50 and 25 pg/g, respectively. The method was successfully applied to the determination of vitamin D3 and its metabolites in the prefrontal cortex, middle frontal cortex, middle temporal cortex, cerebellum, corpus callosum, medulla, and pons of a human brain. All analyzed human brain regions contained 25(OH)D3, with corpus callosum containing 334 pg/g compared with 158 pg/g in cerebellum. 1,25(OH)2D3 was only detected in prefrontal and middle frontal cortices at a very low level. No vitamin D3 was detected in any examined areas of this single human brain.ConclusionsTo the best of our knowledge, this study is the first report of the measurement of concentrations of vitamin D metabolites in human brain. This validated method can be applied to postmortem studies to obtain accurate information about the presence and role of vitamin D and its metabolites in human brain and neurodegenerative diseases.

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Renal effect of vitamin D metabolites: evidence for the essential role of the 25(OH) group

AJP Renal Physiology ◽

10.1152/ajprenal.1983.244.6.f674 ◽

1983 ◽

Vol 244 (6) ◽

pp. F674-F678 ◽

Cited By ~ 1

Author(s):

M. M. Friedlaender ◽

Z. Kornberg ◽

H. Wald ◽

M. M. Popovtzer

Keyword(s):

Vitamin D ◽

Vitamin D3 ◽

Essential Role ◽

Fractional Excretion ◽

Vitamin D Metabolites ◽

Group 2 ◽

Fractional Excretion Of Phosphate ◽

Group 1

The effects of 1 alpha (OH)vitamin D3 [1 alpha (OH)D3] and 24,25(OH)2vitamin D3 [24,25(OH)2D3] on the phosphaturic action of parathyroid hormone (PTH) were studied in two groups of parathyroidectomized (PTX) rats. In group 1, PTX PTH-infused rats received intravenous 1 alpha (OH)D3, and in group 2, PTX PTH-infused rats received intravenous 24,25(OH)2D3. PTX PTH-infused rats served as controls. The effects of both vitamin D metabolites on renal PTH-activated adenylate cyclase (AC) were studied in vitro. In group 1, PTH increased fractional excretion of phosphate (CP/CIn) from 0.045 +/- 0.012 (+/- SE) to 0.263 +/- 0.011 (P less than 0.005). 1 alpha (OH)D3 failed to influence this response. In group 2, PTH increased CP/CIn from 0.055 +/- 0.008 to 0.289 +/- 0.027 (P less than 0.005). 24,25(OH)2D3 reduced the PTH-induced rise in CP/CIn from 0.289 +/- 0.027 to 0.192 +/- 0.021 (P less than 0.01) and decreased the urinary excretion of adenosine 3',5'-cyclic monophosphate. In vitro, 24,25(OH)2D3 blunted the PTH-activated AC, whereas 1 alpha (OH)D3 had no effect. These results show that 24,25(OH)D3, similar to two other 25(OH) metabolites of vitamin D-25(OH)vitamin D3 and 1,25(OH)2vitamin D3-suppresses the phosphaturic action of PTH, whereas 1 alpha(OH)D3, which is devoid of a 25(OH) group, lacks this effect. This suggests that a 25(OH) group is a prerequisite for the antiphosphaturic effect of vitamin D, whereas the 1 alpha (OH) group is not essential for this action.

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Super-doses of dietary vitamin D3 intake in aged laying hens illustrates limitation of 24,25-dihydroxycholecalciferol conversion

10.1101/2021.10.14.464328 ◽

2021 ◽

Author(s):

Matthew F. Warren ◽

Pete M. Pitman ◽

Dellila D. Hodgson ◽

Kimberly A. Livingston

Keyword(s):

Vitamin D ◽

Vitamin D3 ◽

Laying Hens ◽

Dietary Vitamin ◽

Plasma Vitamin ◽

Vitamin D Metabolites ◽

Vitamin D Status ◽

Blood Calcium ◽

Reduce Risk ◽

Dietary Vitamin D

Background: Humans take vitamin D supplements to reduce risk of vitamin D deficiency and reduce the risk of osteoporosis. However, it is unclear how dietary super-dose (10,000x greater than requirement) can affect vitamin D status in aged animals. Aged laying hens could potentially be a model to compare with women in peri- or postmenopausal stages of life because their bone health is physiologically taxed from egg production and they are highly susceptible to osteoporosis. Objective: We investigated dietary super-dose impacts of cholecalciferol (vitamin D3) on vitamin D status in aged laying hens in production. Methods: Forty-eight 68-wk old Hy-Line Brown laying hens were individually housed in cages with eight hens per dietary treatment for eleven weeks. Hens were randomly assigned to one of six groups of dietary vitamin D3 supplementation and fed ad libitum. Supplementation levels were 400 (recommended dosage for hens), 800, 7,400, 14,000, 20,000, and 36,000 IU D3/kg of feed. At termination of the study, all hens were euthanized and we collected blood, feces, and tibia and humerus bones. Ionized (free) blood calcium, fecal calcium, bone calcium, and plasma vitamin D metabolites were measured. Results: We did not discern any dietary effects in tissue and fecal calcium. We observed that increasing dietary vitamin D3 increased plasma vitamin D3, 25-hydroxycholecalciferol, and 24,25-dihydroxycholecalciferol concentrations (p < 0.0001 for all 3 metabolites). We also observed super-dose fed hens had decreased kidney 24-hydroxylase expression (p = 0.0006). Conclusions: Although dietary vitamin D3 super-doses did not affect calcium status in our aged laying hens, it is possible there is an age-related effect of not being as sensitive to vitamin D efficacy. We suggest future research should explore how 24-hydroxylation mechanisms are affected by vitamin D supplementation. Further understanding of 24-hydroxylation can help ascertain ways to reduce risk of vitamin D toxicity.

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Early effects of vitamin D metabolites on phosphate fluxes in isolated rat enterocytes

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1985.248.1.g40 ◽

1985 ◽

Vol 248 (1) ◽

pp. G40-G45 ◽

Cited By ~ 1

Author(s):

G. Karsenty ◽

B. Lacour ◽

A. Ulmann ◽

E. Pierandrei ◽

T. Drueke

Keyword(s):

Vitamin D ◽

Vitamin D3 ◽

Vitamin D Metabolites ◽

Dihydroxyvitamin D3 ◽

Nongenomic Action ◽

Efflux Rate Constant ◽

Membrane Effects ◽

Uptake Velocity ◽

Vitro Effect

The present studies were designed to explore the possibility that, in addition to its well-known steroidlike action, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active vitamin D3 metabolite, modulates inorganic phosphate (Pi) transport across the intestinal mucosa through more rapid membrane effects. Enterocytes were mechanically isolated from the duodenojejunum of vitamin D-replete rats. In this model enterocyte Pi uptake was a temperature-dependent as well as a Na+-dependent process. In vitro addition of 1,25(OH)2D3 (1 pM) led to a significant increase in Na+-dependent initial Pi uptake velocity (iVpi) within 20 min (P less than 0.001). No effect was seen for shorter incubation times (5 and 15 min). Incubation of the cells with cycloheximide did not inhibit the hormone-mediated increase of iVpi. 25-Hydroxyvitamin D3 significantly increased iVPi (P less than 0.05) at a concentration of 1 nM but not 1 pM. Vitamin D3 at a concentration of 1 microM had no effect on iVPi. Enterocyte Pi efflux rate constant was not modified by the presence of 1,25(OH)2D3(1pM). Thus, the early in vitro effect of 1,25(OH)2D3 on Pi uptake by isolated enterocytes suggests a nongenomic action of the hormone, possibly by modifying the lipid structure of the plasma membrane.

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Biological activity assessment of the vitamin D metabolites 1,25-dihydroxy-24-oxo-vitamin D3 and 1,23,25-trihydroxy-24-oxo-vitamin D3

Archives of Biochemistry and Biophysics ◽

10.1016/0003-9861(83)90254-0 ◽

1983 ◽

Vol 224 (2) ◽

pp. 671-676 ◽

Cited By ~ 20

Author(s):

Eberhard Mayer ◽

June E. Bishop ◽

Norio Ohnuma ◽

Anthony W. Norman

Keyword(s):

Vitamin D ◽

Biological Activity ◽

Vitamin D3 ◽

Vitamin D Metabolites ◽

Activity Assessment

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Cathelicidin, vitamin D3 dan imunitas terhadap tuberkulosis

Jurnal Kedokteran Syiah Kuala ◽

10.24815/jks.v20i3.18610 ◽

2020 ◽

Vol 20 (3) ◽

Author(s):

Yunita Arliny ◽

Maryatun Hasan

Keyword(s):

Vitamin D ◽

Immune Response ◽

Innate Immune Response ◽

Vitamin D3 ◽

Immune Cells ◽

Active Form ◽

Innate Immune ◽

Dihydroxyvitamin D3 ◽

1,25 Dihydroxyvitamin D3 ◽

Natural Defense

Abstrak. Tuberkulosis (TB) merupakan salah satu penyakit infeksi yang menjadi masalah di dunia. Risiko untuk mendapatkan infeksi TB dipengaruhi oleh imunitas alamiah melawan mikobakteria. Peptida antimikroba merupakan salah satu barrier pertahanan alamiah. Cathelicidin adalah suatu peptida anti mikroba yang berperan pada proses imunitas terhadap TB. Cathelicidin Leusin Leusin-37 (LL-37) merupakan satu-satunya cathelicidin yang ada pada manusia dan dapat diekspresikan dari beberapa sel temasuk sel imun. Inducer Cathelicidin yang paling poten adalah 1,25-dihydroxyvitamin D3 yang merupakan bentuk aktif vitamin D 25(OH)D3. Tinjauan pustaka ini membahas tentang cathelicidin, vitamin D3 dam peranannya pada imunitas terhadap TB.Kata kunci: Cathelicidin, 1,25-dihydroxyvitamin D3, vitamin D 25(OH)2D3, imunitas, TuberkulosisAbstract. Tuberculosis is one of the most important infectious diseases worldwide. The susceptibility to this disease depends to great extent on the innate immune response against mycobacteria. Antimicrobial peptides are one of the natural defense barriers. Cathelicidin Leucine Leucine-37 (LL-37) is the only cathelicidin present in humans and synthesized by several cells including immune cells. The most effective inducer of Cathelicidin is 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3), which is an active form of vitamin D 25(OH)D3. This review discusses cathelicidin, vitamin D3 and its role in immunity against TBKeywords: Cathelicidin, 1,25-dihydroxyvitamin D3, vitamin D 25(OH)D3, immunity, Tuberkulosis

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INFLUENCE OF ULTRAVIOLET BLOOD IRRADIATION ON COVID-19 ASSOCIATED COMMUNITY-ACQUIRED PNEUMONIA

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-iou-1610 ◽

2021 ◽

Author(s):

I. Khodza ◽

P. Puzdryak ◽

P Bondarenko ◽

A. Degtyarev ◽

A. Erofeev ◽

...

Keyword(s):

Immune Response ◽

Interleukin 6 ◽

High Efficiency ◽

Community Acquired Pneumonia ◽

Medical Community ◽

Dna Molecules ◽

Coronavirus Infection ◽

Blood Irradiation ◽

Anti Inflammatory ◽

Positive Effect

The pandemic of 21st century caused by the SARS-Cov-2 virus has posed a challenge for the global medical community. Community-acquired polysegmental pneumonia caused by the novel coronavirus infection (COVID-19) proceeds in a variety of types and may be complicated by a potentially lethal immune response - a cytokine storm. The latter is characterized by rapid proliferation and increased activity of T-cells, macrophages and natural killer cells releasing various inflammatory cytokines and chemical mediators by protective cells [5,8]. This pathological condition can be treated by recombinant humanized monoclonal antibody against monofunctional cytokine human interleukin-6 receptor. The effect of IL-6 blockers is to selectively bind and inhibit both soluble and membrane IL-6 receptors (sIL-6R and mIL-6R). There are studies demonstrating a positive effect and increased survival rate while using drugs that block the production of interleukin-6 [7,11]. The new coronavirus infection causes inflammation of the artery wall with intravascular thrombogenesis, which justifies the high efficiency of anticoagulant and hormone therapy [6,9,10].The standards of drug treatment of the studied infection include antiviral, anti-inflammatory, anticoagulant, mucolytic, symptomatic, intravenous infusion and oxygen therapy.Methodological recommendations for the diagnosis and treatment of a new coronavirus infection, issued by the Ministry of Health of the Russian Federation, are regularly updated in accordance with the accumulation of positive treatment results by global and local medical communities. In addition to drug therapy, there are other methods of body detoxification. One of the additional methods for treatment of community-acquired pneumonia along with viral "vasculitis" and correction of the immune response can be provided by ultraviolet blood irradiation (UBI).It is well known that ultraviolet radiation has a disinfecting effect. The wavelengths used in UVBI affect the efficiency of UV absorption by DNA molecules of the pathogen. Bactericidal UV radiation at certain wavelengths causes thymine dimerization in DNA molecules. The accumulation of such changes in the DNA of microorganisms leads to a slowdown in the rate of their reproduction and extinction. The photohemocorrection method is characterized by immunostimulatory, anti-inflammatory, anti-hypoxic, membrane stabilizing, antioxidant and detoxifying effects [1]. In the current study we obtained data on a significant decrease in the systemic inflammatory response, marked and fast decrease of the C-reactive protein in blood tests of patients while receiving ultraviolet blood irradiation. The relief of the systemic inflammatory reaction had a positive effect on the reduction of infiltrative changes in the lung tissue, as well as the timing of discharge from hospital.

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