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Omeprazole suppressed plasma magnesium level and duodenal magnesium absorption in male Sprague-Dawley rats

  • Integrative physiology
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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 PO4 3− 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.

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Acknowledgements

This study was supported by the research grants from the Thailand Research Fund (RSA5680005), Burapha University through National Research Council of Thailand (33/2559), and the Faculty of Allied Health Sciences, Burapha University (AHS08/2558) to N. Thongon. We express our gratitude to Emeritus Prof. Dr. Prasert Sobhon of the Facuty of Allied Health Sciences, Burapha University, for his helpful suggestions and proofreading. We also thank Asst. Prof. Dr. Siriporn Chamniansawat, Ms. Maneerat Sakuntang, Ms. Sariya Ragsanit, Ms. Warintip Wetkama of the Facuty of Allied Health Sciences, Burapha University, Ms. Pornpun Seelaphong of the Microscopic Center, Faculty of Science, Burapha University, and Mr. Sakorn Praiwijarn and Ms. Dokerug Suwanchalong of Medical Laboratory Center, Burapha University Hospital, Burapha University for their excellent technical assistance.

Author contributions

Thongon N designed and performed experiments, analyzed and interpreted the results, wrote and edited the manuscript. Penguy J, Kulwong S, Khongmueang K, and Thongma M performed experiments.

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  1. Division of Physiology, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, 169 Long-Hard Bangsaen Rd., Saensook, Muang, Chonburi, 20131, Thailand

    Narongrit Thongon, Jirawat Penguy, Sasikan Kulwong, Kanyanat Khongmueang & Matthana Thongma

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  1. Narongrit Thongon
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Thongon, N., Penguy, J., Kulwong, S. et al. Omeprazole suppressed plasma magnesium level and duodenal magnesium absorption in male Sprague-Dawley rats. Pflugers Arch - Eur J Physiol 468, 1809–1821 (2016). https://doi.org/10.1007/s00424-016-1905-7

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