Published online Mar 21, 2020. doi: 10.3748/wjg.v26.i11.1142
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
Dietary intake is the sole source of Mg2+ in humans, and intestinal absorption plays a vital role in the regulation of normal Mg2+ balance. Previous case reports suggested that intestinal Mg2+ malabsorption is a major pathophysiological mechanism in proton pump inhibitor (PPI)-induced hypomagnesemia (PPIH).
The exact mechanism of PPI-inhibited intestinal Mg2+ absorption is still controversial. In addition, a simultaneous study on transcellular and paracellular Mg2+ absorption in the duodenum, jejunum, ileum, and colon of normal and PPIH had not been performed.
The present study aimed to observe the rate of paracellular and transcellular Mg2+ transport across the duodenum, jejunum, ileum, and colon in control and prolonged omeprazole-treated male Sprague-Dawley rats. Magnesiotropic hormones and proteins were measured.
The rats received subcutaneous omeprazole injection for 12 or 24 wk. The duodenum, jejunum, ileum, and colon of each rat were mounted onto individual modified Ussing chamber setups to study the rates of total, transcellular, and paracellular Mg2+ absorption simultaneously. Magnesiotropic hormones and proteins were observed.
Hypomagnesemia and hypomagnesuria were demonstrated in the PPIs-treated rats. Plasma 1α,25-dihydroxyvitamin D3 and fibroblast growth factor 23 increased, whereas plasma epidermal growth factor level decreased in the omeprazole-treated rats. We clearly showed paracellular and transcellular Mg2+ absorption in the duodenum, jejunum, ileum, and colon of the control rats. Prolonged PPI treatment significantly inhibited transcellular and paracellular Mg2+ absorption in the duodenum, jejunum, ileum, and colon. High transient receptor potential melastatin 6 and cyclin M4 expression in the entire intestinal tract of the PPI-treated rats were demonstrated.
Prolonged PPI administration markedly inhibits Mg2+ absorption throughout the entire length of intestinal tract and lead to systemic Mg2+ deficiency.
PPIs mainly suppressed Mg2+ absorption in the small intestine. The stimulation of small intestinal Mg2+ absorption is probably nullifying the adverse effect of PPIs in chronic users.