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Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Pflugers+Arch 2016 ; 468 (11-12): 1809-1821 Nephropedia Template TP
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Omeprazole suppressed plasma magnesium level and duodenal magnesium absorption in male Sprague-Dawley rats #MMPMID27866273
Thongon N; Penguy J; Kulwong S; Khongmueang K; Thongma M
Pflugers Arch 2016[Nov]; 468 (11-12): 1809-1821 PMID27866273show ga
Hypomagnesemia is the most concerned side effect of proton pump inhibitors (PPIs) in chronic users. However, the mechanism of PPIs-induced systemic Mg(2+) deficit is currently unclear. The present study aimed to elucidate the direct effect of short-term and long-term PPIs administrations on whole body Mg(2+) homeostasis and duodenal Mg(2+) absorption in rats. Mg(2+) homeostasis was studied by determining the serum Mg(2+) level, urine and fecal Mg(2+) excretions, and bone and muscle Mg(2+) contents. Duodenal Mg(2+) absorption as well as paracellular charge selectivity were studied. Our result showed that gastric and duodenal pH markedly increased in omeprazole-treated rats. Omeprazole significantly suppressed plasma Mg(2+) level, urinary Mg(2+) excretion, and bone and muscle Mg(2+) content. Thus, omeprazole induced systemic Mg(2+) deficiency. By using Ussing chamber techniques, it was shown that omeprazole markedly suppressed duodenal Mg(2+) channel-driven and Mg(2+) channel-independent Mg(2+) absorptions and cation selectivity. Inhibitors of mucosal HCO(3)(-) secretion significantly increased duodenal Mg(2+) absorption in omeprazole-treated rats. We therefore hypothesized that secreted HCO(3)(-) in duodenum decreased luminal proton, this impeded duodenal Mg(2+) absorption. Higher plasma total 25-OH vitamin D, diuresis, and urine PO(4)(3-) were also demonstrated in hypomagnesemic rats. As a compensatory mechanism for systemic Mg(2+) deficiency, the expressions of duodenal transient receptor potential melastatin 6 (TRPM6), cyclin M4 (CNNM4), claudin (Cldn)-2, Cldn-7, Cldn-12, and Cldn-15 proteins were enhanced in omeprazole-treated rats. Our findings support the potential role of duodenum on the regulation of Mg(2+) homeostasis.
Pflugers+Arch 2016 ; 468 (11-12): 1809-1821
