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Title: Effects of Lead on Vitamin D Metabolism in Rats
Authors: Ameena Abdullah Al-Awadhi 
Supervisor: Dr. Abdur Rahman Ahmad
Keywords: 25-hydroxyvitamin D : Alzheimer disease
Issue Date: 2017
Publisher:  Kuwait university - college of graduate studies
Abstract: Vitamin D deficiency and high blood lead levels (BPbLs) have both become more prevalent, and both are known to affect brain development and function. A negative association between BPbLs and vitamin D has been reported, suggesting that lead (Pb) interferes with vitamin D metabolism and function. We investigated the effects of Pb on serum level of two vitamin D metabolites, 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D], two vitamin D metabolizing enzymes, 25-hydroxylase and 1-α-hydroxylase, and vitamin D receptor (VDR). Newborn Wistar rat pups were exposed to 0.2% Pb acetate via their dams’ drinking water from post-natal day (PND) 1 to 21 and directly in drinking water until PND30. Serum 25(OH)D was analyzed with LC-MS/MS and 1,25(OH)2D with a 3-step sandwich chemiluminescent immunoassay. BPbL was measured with ICP-OES. Expression of 25-hydroxylase, 1-α-hydroxylase, and VDR was measured by Western blot and immunohistochemistry. Serum 25(OH)D decreased from 32.16 ± 7.46 nmol/L in control rat pups to 23.27 ± 5.71 nmol/L in Pb-exposed rats at PND21, and from 32.15 ± 6.33 to 26.96 ± 6.37 nmol/L respectively at PND30 (p < 0.05). Serum 1,25 (OH)2 D was decreased by Pb only at PND21 (428.84 ± 132.84 pmol/L in control vs 361.49 ± 83.63 pmol/L in Pb-exposed; p < 0.05), whereas it was not significantly affected at PND30. The results of the 1,25(OH)2 D were parallel to the effect of Pb on the expression of 1-α-hydroxylase in kidney, which was significantly decreased only at PND21 (p < 0.05). Brain 1-α-hydroxylase expression was not affected by Pb either at PND21 or at PND30 (p > 0.05). Hepatic 25-hydroxylase expression was decreased by 20.6% (p < 0.05) at PND21 but significantly increased at PND30 by 33.4% (p < 0.05). VDR expression in the brain was significantly increased at both PND21 and PND30, by 19.7 and 28.57%, respectively (p < 0.05). Similar expression pattern of the 25-hydroxylase, 1-α-hydroxylase and VDR was also observed by immunohistochemistry. These results suggest that Pb interferes with vitamin D metabolism by affecting the expression of its metabolizing enzymes. The effects on 1-α-hydroxylase appears to be tissue specific, whereas, the effect of Pb on 25-hydroxylase depends on the developmental stage of the rat. Further research is needed to elucidate the biochemical mechanism(s) of these effects and their physiological relevance.
Appears in Programs:1820 Nutrition Science & Food Science

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