Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2020; 26(11): 1142-1155
Published online Mar 21, 2020. doi: 10.3748/wjg.v26.i11.1142
Effect of prolonged omeprazole administration on segmental intestinal Mg2+ absorption in male Sprague-Dawley rats
Nasisorn Suksridechacin, Punnisa Kulwong, Siriporn Chamniansawat, Narongrit Thongon
Nasisorn Suksridechacin, Punnisa Kulwong, Narongrit Thongon, Division of Physiology, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand
Siriporn Chamniansawat, Division of Anatomy, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand
Author contributions: Suksridechacin N performed experiments, analyzed the results, and edited the manuscript; Kulwong P performed experiments; Chamniansawat S performed experiments, analyzed the results, and wrote and edited the manuscript; Thongon N designed and performed experiments, analyzed and interpreted the results, and wrote and edited the manuscript.
Supported by Burapha University through National Research Council of Thailand, No. 15/2562.
Institutional review board statement: This study was reviewed and approved by Institutional Review Committee ( ID# 23/2559).
Institutional animal care and use committee statement: This study was approved by the Ethics Committee on Animal Experiment of Burapha University, Thailand.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: The data could be downloaded from the public databases, and no additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Narongrit Thongon, PhD, Associate Professor, Division of Physiology, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, No. 169 Long-Hard Bangsaen Road, Saensook, Muang, Chonburi 20131, Thailand. narongritt@buu.ac.th
Received: November 18, 2019
Peer-review started: November 18, 2019
First decision: January 19, 2020
Revised: February 6, 2020
Accepted: March 5, 2020
Article in press: March 5, 2020
Published online: March 21, 2020
Abstract
BACKGROUND

The exact mechanism of proton pump inhibitors (PPIs)-induced hypomagnesemia (PPIH) is largely unknown. Previous studies proposed that PPIH is a consequence of intestinal Mg2+ malabsorption. However, the mechanism of PPIs-suppressed intestinal Mg2+ absorption is under debate.

AIM

To investigate the effect of 12-wk and 24-wk omeprazole injection on the total, transcellular, and paracellular Mg2+ absorption in the duodenum, jejunum, ileum, and colon of male Sprague-Dawley rats.

METHODS

The rats received 20 mg/kg∙d subcutaneous omeprazole injection for 12 or 24 wk. Plasma and urinary Mg2+, Ca2+, and PO43− levels were measured. The plasma concentrations of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23), epidermal growth factor (EGF), and insulin were also observed. The duodenum, jejunum, ileum, and colon of each rat were mounted onto individual modified Using chamber setups to study the rates of total, transcellular, and paracellular Mg2+ absorption simultaneously. The expression of transient receptor potential melastatin 6 (TRPM6) and cyclin M4 (CNNM4) in the entire intestinal tract was also measured.

RESULTS

Single-dose omeprazole injection significantly increased the intraluminal pH of the stomach, duodenum, and jejunum. Omeprazole injection for 12 and 24 wk induced hypomagnesemia with reduced urinary Mg2+ excretion. The plasma Ca2+ was normal but the urinary Ca2+ excretion was reduced in rats with PPIH. The plasma and urinary PO43− levels increased in PPIH rats. The levels of 1α,25(OH)2D3 and FGF-23 increased, whereas that of plasma EGF decreased in the omeprazole-treated rats. The rates of the total, transcellular, and paracellular Mg2+ absorption was significantly lower in the duodenum, jejunum, ileum, and colon of the rats with PPIH than in those of the control rats. The percent suppression of Mg2+ absorption in the duodenum, jejunum, ileum, and colon of the rats with PPIH compared with the control rats was 81.86%, 70.59%, 69.45%, and 39.25%, respectively. Compared with the control rats, the rats with PPIH had significantly higher TRPM6 and CNNM4 expression levels throughout the intestinal tract.

CONCLUSION

Intestinal Mg2+ malabsorption was observed throughout the intestinal tract of rats with PPIH. PPIs mainly suppressed small intestinal Mg2+ absorption. Omeprazole exerted no effect on the intraluminal acidic pH in the colon. Thus, the lowest percent suppression of total Mg2+ absorption was found in the colon. The expression levels of TRPM6 and CNNM4 increased, indicating the presence of a compensatory response to Mg2+ malabsorption in rats with PPIH. Therefore, the small intestine is an appropriate segment that should be modulated to counteract PPIH.

Keywords: Adverse effect, Colon, Mg2+ absorption, Proton pump inhibitors-induced hypomagnesemia, Small intestine

Core tip: Proton pump inhibitors (PPIs) induced hypomagnesemia (PPIH) has attracted attention in the past decade. Previous studies proposed that PPIH is a consequence of intestinal Mg2+ malabsorption. However, the effect of prolonged PPI administration on duodenal, jejunal, ileal, and colonic Mg2+ absorption is largely unknown. In this study, the rats received 20 mg/ kg∙d subcutaneous omeprazole injection for 12 and 24 wk, which is comparable to 5 and 10 human years, respectively. Omeprazole injection induced hypomagnesemia with reduced urinary Mg2+ excretion. The rates of total, paracellular, and transcellular Mg2+ absorption reduced in the duodenum, jejunum, ilium, and colon were discovered in PPIH rats.