title: Omeprazole suppressed plasma magnesium level and duodenal magnesium absorption in male Sprague-Dawley rats.
abstract: Hypomagnesemia is the most concerned side effect of proton pump inhibitors (PPIs) in chronic users. However, the mechanism of PPIs-induced systemic Mg2+deficit is currently unclear. The present study aimed to elucidate the direct effect of short-term and long-term PPIs administrations on whole body Mg2+homeostasis and duodenal Mg2+absorption in rats. Mg2+homeostasis was studied by determining the serum Mg2+level, urine and fecal Mg2+excretions, and bone and muscle Mg2+contents. Duodenal Mg2+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 Mg2+level, urinary Mg2+excretion, and bone and muscle Mg2+content. Thus, omeprazole induced systemic Mg2+deficiency. By using Ussing chamber techniques, it was shown that omeprazole markedly suppressed duodenal Mg2+channel-driven and Mg2+channel-independent Mg2+absorptions and cation selectivity. Inhibitors of mucosal HCO3-secretion significantly increased duodenal Mg2+absorption in omeprazole-treated rats. We therefore hypothesized that secreted HCO3-in duodenum decreased luminal proton, this impeded duodenal Mg2+absorption. Higher plasma total 25-OH vitamin D, diuresis, and urine PO43-were also demonstrated in hypomagnesemic rats. As a compensatory mechanism for systemic Mg2+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 Mg2+homeostasis.
authors.affiliation: Division of Physiology, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, 169 Long-Hard Bangsaen Rd., Saensook, Muang, Chonburi, 20131, Thailand. narongritt@buu.ac.th.
authors.forename: Narongrit
authors.initials: N
authors.lastname: Thongon
authors.affiliation: Division of Physiology, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, 169 Long-Hard Bangsaen Rd., Saensook, Muang, Chonburi, 20131, Thailand.
authors.forename: Jirawat
authors.initials: J
authors.lastname: Penguy
authors.affiliation: Division of Physiology, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, 169 Long-Hard Bangsaen Rd., Saensook, Muang, Chonburi, 20131, Thailand.
authors.forename: Sasikan
authors.initials: S
authors.lastname: Kulwong
authors.affiliation: Division of Physiology, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, 169 Long-Hard Bangsaen Rd., Saensook, Muang, Chonburi, 20131, Thailand.
authors.forename: Kanyanat
authors.initials: K
authors.lastname: Khongmueang
authors.affiliation: Division of Physiology, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, 169 Long-Hard Bangsaen Rd., Saensook, Muang, Chonburi, 20131, Thailand.
authors.forename: Matthana
authors.initials: M
authors.lastname: Thongma
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000009:adverse effects / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000378:metabolism; D057167:Claudins / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects*; D008274:Magnesium / Q000097:blood / Q000378:metabolism*; D008275:Magnesium Deficiency / Q000209:etiology*; D008297:Male; D009853:Omeprazole / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050053:TRPM Cation Channels / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; D027682:Cation Transport Proteins; D057167:Claudins; C530931:Cnnm4 protein, rat; D050053:TRPM Cation Channels; C507531:TRPM6 protein, rat; D008274:Magnesium; D009853:Omeprazole
keywords: Hypomagnesemia; Intestinal Mg2+absorption; Mg2+ homeostasis; Proton pump inhibitors; Ussing chamber