Effects of the Administration of 25(OH) Vitamin D3 in an Experimental Model of Chronic Kidney Disease in Animals Null for 1-Alpha-Hydroxylase

Torremadé, Noelia; Božić, Milica; Goltzman, David; Fernàndez, Elvira; Valdivielso, José M.

doi:10.1371/journal.pone.0170654

Cited by 8 publications

(5 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The current study found that on day 6 after MTX chemotherapy, there was a significant increase in TRPV6 gene expression (as well as a trend of an increase in CALBINDIND9K expression) in the small intestine, suggesting presence of increased demand for Ca absorption locally in the intestine early after chemotherapy. This situation is analogous to increased expression levels of genes (TRPV5 and calbindinD-28K) responsible for Ca reabsorption in the proximal tubules of the kidney observed in mice with experimental chronic kidney disease [58]. Interestingly, the current study also found that the increased expression of TRPV6 and CALBINDIND9K on day 6 returned to normal levels on days 9 and 14, suggesting normalisation (during the later stage) of the intestinal calcium absorption demand (increased in the early stage).…”

Section: Discussionsupporting

confidence: 80%

Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation

Su,

Lee,

et al. 2023

Cancers

View full text Add to dashboard Cite

Vitamin D deficiency or insufficiency is prevalent in childhood cancer patients and survivors after chemotherapy; further studies are needed to investigate the underlying aetiology and effectiveness of vitamin D supplementation in preventing chemotherapy-induced bone loss. This study used a rat model of treatment with antimetabolite methotrexate to investigate whether methotrexate chemotherapy causes vitamin D deficiency and if vitamin D supplementation attenuates the resultant bone loss. Methotrexate treatment (five daily injections) decreased serum vitamin D levels (from 52 to <30 ng/mL), reduced body and bone lengthening and tibial trabecular bone volume, and altered intestinal vitamin D metabolism, which was associated with intestinal mucosal damage known to cause malabsorption of nutrients, including dietary vitamin D and calcium. During the early stage after chemotherapy, mRNA expression increased for vitamin D activation enzyme CYP27B1 and for calcium-binding protein TRPV6 in the intestine. During the intestinal healing stage, expression of vitamin D catabolism enzyme CYP24 increased, and that of TRPV6 was normalised. Furthermore, subcutaneous calcitriol supplementation diminished methotrexate-induced bone loss due to its effect suppressing methotrexate-induced increased bone resorption. Thus, in young rats, methotrexate chemotherapy causes vitamin D deficiency, growth impairments, bone loss, and altered intestinal vitamin D metabolism, which are associated with intestinal damage, and vitamin D supplementation inhibits methotrexate-induced bone loss.

show abstract

Section: Discussionsupporting

confidence: 80%

Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation

Su,

Lee,

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…Although 25 VD has been considered for a long time an inactive reservoir of 1,25 VD, a growing body of evidence indicates that it has its own biological activities in different tissues, including skeletal muscle . The presence of Cyp27b1 in skeletal muscle cells would suggest, as a mechanism of action of 25 VD, its intracellular conversion to 1,25 VD by 25 VD‐1α‐hydroxylase, a process indeed occurring in T cell response to 25 VD .…”

Section: Discussionmentioning

confidence: 99%

Opposing effects of 25‐hydroxy‐ and 1α,25‐dihydroxy‐vitamin D₃ on pro‐cachectic cytokine‐and cancer conditioned medium‐induced atrophy in C2C12 myotubes

et al. 2019

View full text Add to dashboard Cite

Aim: Loss of skeletal muscle is one of the main features of cancer cachexia. Vitamin D (VD) deficiency is associated with impairment of muscle mass and performance and is highly prevalent in cachectic patients; therefore, VD supplementation has been proposed to counteract cancer cachexia-associated muscle loss. However, in both cachectic cancer patients and tumour-bearing animals, VD supplementation led to disappointing results, urging the need for a better understanding of VD activity on skeletal muscle. Methods: Cancer-associated muscle wasting was reproduced in vitro by treating C2C12 myotubes with cancer cell conditioned medium, a combination of TNF-α and IFNγ or IL-6 pro-cachectic cytokines. The biological effects and mechanisms of action of 1,25-dihydroxy VD (1,25 VD) and its precursor 25-hydroxy VD (25 VD) on myotubes were explored. Results: We demonstrated that only 25 VD was able to protect from atrophy by activating Akt signalling, inducing protein synthesis, and stimulating the autophagic flux, while 1,25 VD had an atrophic activity per se, increasing FoxO3 levels, inducing the expression of atrogenes, and blocking the autophagic flux. Furthermore, we showed that the contrasting activities of these VD metabolites on C2C12 myotubes depend on a differential induction of VD-24-hydroxylase and transformation of VD metabolites in pro-atrophic 24-hydroxylated products, as silencing of VD-24-hydroxylase reduced the atrophic activity of 1,25 VD. Conclusions: Altogether these data might explain the lack of efficacy of VD treatment in vivo for the protection of muscle mass in cancer. K E Y W O R D Satrogenes, autophagy, cancer cachexia, Cyp24a1 24-hydroxylase, Cyp27b1 1α-hydroxylase, skeletal muscle atrophy 2 of 10 | SUSTOVA eT Al.

show abstract

“…For example, Aloia et al [ 27 ] and Hansen et al [ 28 ] reported that plain vitamin D3 administration was not effective or induced only small increases in FCA in a high-dose group [ 28 ]. Recent reports indicated that CYP27B1 expression occurred in duodenal cells, suggesting that after 25-hydroxylation of plain vitamin D3 in the liver, 25(OH)D3 may be converted to calcitriol in the duodenum [ 29 , 30 ]. The other possible explanation for the poor FCA response to plain vitamin D3 treatment is that plain vitamin D3 can only stimulate FCA once a threshold serum concentration of calcitriol is achieved.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of intestinal calcium absorption by orally administrated vitamin D3 compounds: a prospective open-label randomized trial in osteoporosis

Uenishi

Tokiwa²,

Kato

et al. 2017

Osteoporos Int

View full text Add to dashboard Cite

SummaryIntestinal fractional calcium absorption (FCA) was assessed before and after vitamin D3 treatment. Serum 1,25(OH)2D concentration was significantly increased by plain vitamin D3 and reduced by eldecalcitol. The 1α hydroxyl calcidiol and eldecalcitol treatments increased FCA, which may be induced through direct stimulation of vitamin D receptors in the intestine.IntroductionTo assess the effects of vitamin D3 compounds on intestinal FCA and calcium-regulating hormones in post-menopausal osteoporosis, a randomized open-label prospective study was conducted.MethodsForty eligible patients were allocated randomly into four groups: eldecalcitol (ELD; 0.75 μg/day), 1α hydroxyl calcidiol (ALF; 1 μg/day), plain vitamin D3 (800 IU/day), and control. Before and after the 4-week treatment, intestinal FCA was estimated by using a double isotope method, and serum concentrations of calcium-regulating hormones and a bone turnover marker were measured.ResultsThe baseline FCA value of the participants was 21.5 ± 7.9% (mean ± SD) and was significantly correlated with serum 1,25(OH)2D (calcitriol) concentration. After the treatment, the FCA significantly increased by 59.5% (95% CI, 41.6 to 77.4%) in the ELD group and by 45.9% (27.9 to 63.8%) in the ALF group, whereas no significant change in the plain vitamin D3 group was found. Unlike the baseline FCA, post-treatment FCA exhibited no significant correlation with serum calcitriol concentration. Parathyroid hormone levels were suppressed by ALF and plain vitamin D3 but were sustained in the ELD and control groups. Serum calcitriol tended to be suppressed by ELD, whereas plain vitamin D3 treatment increased both serum 25(OH)D and calcitriol concentrations.ConclusionThese findings suggest that oral administration of vitamin D3 analogues (ALF and ELD) stimulates FCA but plain vitamin D3 does not. Those effects of vitamin D3 compounds on FCA were independent of serum calcitriol concentration, suggesting that ALF and ELD may directly stimulate intestinal vitamin D receptors.

show abstract

Effects of the Administration of 25(OH) Vitamin D3 in an Experimental Model of Chronic Kidney Disease in Animals Null for 1-Alpha-Hydroxylase

Cited by 8 publications

References 39 publications

Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation

Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation

Opposing effects of 25‐hydroxy‐ and 1α,25‐dihydroxy‐vitamin D₃ on pro‐cachectic cytokine‐and cancer conditioned medium‐induced atrophy in C2C12 myotubes

Stimulation of intestinal calcium absorption by orally administrated vitamin D3 compounds: a prospective open-label randomized trial in osteoporosis

Contact Info

Product

Resources

About

Effects of the Administration of 25(OH) Vitamin D3 in an Experimental Model of Chronic Kidney Disease in Animals Null for 1-Alpha-Hydroxylase

Cited by 8 publications

References 39 publications

Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation

Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation

Opposing effects of 25‐hydroxy‐ and 1α,25‐dihydroxy‐vitamin D3 on pro‐cachectic cytokine‐and cancer conditioned medium‐induced atrophy in C2C12 myotubes

Stimulation of intestinal calcium absorption by orally administrated vitamin D3 compounds: a prospective open-label randomized trial in osteoporosis

Contact Info

Product

Resources

About

Opposing effects of 25‐hydroxy‐ and 1α,25‐dihydroxy‐vitamin D₃ on pro‐cachectic cytokine‐and cancer conditioned medium‐induced atrophy in C2C12 myotubes