Simultaneous Exposure of Excess Fluoride and Calcium Deficiency Alters VDR, CaR, and Calbindin D 9 �k mRNA Levels in Rat Duodenal Mucosa

Abstract

Fluoride ingestion reduces intestinal calcium absorption; its molecular basis has not been studied. We studied the mRNA expression of calcium-sensing receptor (CaR), vitamin D receptor (VDR) and calbindin D 9 k (D 9 k) by northern blot analysis in the duodenal mucosa of rats. Weanling pups fed with chow diet containing adequate calcium (0.5% w/w) and drinking water (NaF < 1 ppm) served as controls (Group I) and were studied at 9 and 15 weeks. The pups, born to rats fed with a calcium-deficient diet (0.03%) and excess fluoride water (NaF 50 ppm), were continued on the same diet and water (Group II) until 9 weeks of age. Subsequently, Group II rats were divided into 4 subgroups; 3 subgroups with fluoride free water [II-A adequate calcium, II-B excess calcium (Ca 2%) and II-D calcium deficient], whereas II-C received fluorinated water and adequate calcium diet until 15 weeks. At 9 weeks, as compared to group-I, group-II had decreased VDR (P < 0.001) and D 9 k mRNA (P < 0.001), whereas CaR mRNA levels increased (P < 0.05). At 15 weeks, as compared to group-I, VDR mRNA further reduced in group II-D (P < 0.001) and II-C (P < 0.001), whereas it increased in group II-A. Removal of fluoride ingestion and calcium replenishment increased D 9 k mRNA expression, maximally in adequate calcium group (P < 0.001), while it was further reduced in group II-C (P < 0.001). CaR expression decreased significantly in all the groups. We conclude that excess fluoride reduces the mRNA levels of VDR and D 9 k in the duodenal mucosa of rats, thereby possibly reducing calcium absorption. Calcium supplementation with simultaneous fluoride removal improves their expression.

Amelioration of chronic fluoride toxicity by calcium and fluoride-free water in rats

“…In phase II, after receiving the NCD, serum 25(OH) vitamin D 3 and 1,25(OH) 2 vitamin D 3 of treatment groups Ca − F − /Ca+F − , Ca − F+/Ca+F − and Ca − F+/Ca+F+ were comparable with other groups. A significant increase in expression of CASR levels in treatment groups Ca − F − (6-fold), Ca+F+(4·5-fold) and Ca − F+(9-fold), as compared with Ca+F − , was observed as reported previously also ( 22 ) . The reason behind significant increases of VDR and S100G expression levels in LCD-treated groups in phase I was Ca insufficiency, in which expression of VDR is up-regulated ( 44 ) .…”

“…1,25(OH) 2 vitamin D 3 alters the transcription of S100 Ca-binding protein G (S100G) in the intestine ( 20 , 21 ) to increase Ca absorption. In a study carried out in rats fed 50 ppm F for 6 weeks, it was found that F exhibited an inhibitory effect on duodenal VDR and S100G gene transcription, thereby reducing Ca absorption ( 22 ) . However, serum parathyroid hormone was not assessed in the study.…”

Impact of subchronic exposure to triclosan and/or fluoride on estrogenic activity in immature female rats: The expression pattern of calbindin‐D9k and estrogen receptor α genes

“…On the contrary, notable downregulation of CaBP‐9k was noticed in the NaF‐treated group. Similarly, it was reported that excess F reduces the mRNA levels of CaBP‐9k in the duodenal mucosa of rats …”

Identification of kaempferol‐regulated proteins in rat calvarial osteoblasts during mineralization by proteomics

“…Our data show that reticulocalbin 3‐EF, a calcium‐binding protein 39 is upregulated in K‐treated osteoblasts. Reticulocalbin has no significant sequence homology with any other proteins except the EF hand motifs; however, the overall structure of reticulocalbin is similar to that of calbindin D 28K and calretinin 40, 41. Although there are reports on the structure and localization of reticulocalbin 42, 43, exact function of this protein remains unknown.…”