Vol.:(0123456789) 1 3 Anatomical Science International https://doi.org/10.1007/s12565-020-00572-w ORIGINAL ARTICLE Ultrastructural intestinal mucosa change after prolonged inhibition of gastric acid secretion by omeprazole in male rats Siriporn Chamniansawat 1  · Nattida Kampuang 2  · Nasisorn Suksridechacin 2  · Narongrit Thongon 2 Received: 11 June 2020 / Accepted: 2 September 2020 © Japanese Association of Anatomists 2020 Abstract Omeprazole is a potent inhibitor of gastric acid secretion. It was reported that omeprazole induced dramatic gastric mucosa morphologic changes from the resting state to the stimulated state. However, the efect of omeprazole administration on the ultrastructure and absorptive function of small intestines was largely unknown. Here, male Sprague–Dawley rats were daily treated with a single dose of omeprazole for 12 or 24 weeks. Ultrastructure intestinal mucosal change in duodenum, jejunum, and ileum was observed. We also determined small intestine infammation, using intraepithelial lymphocytes activation. Finally, magnesium levels were measured in plasma, urine, feces, muscle, and bone to determine systemic magnesium bal- ance. Omeprazole-treated rats had signifcantly decreased the width of tight junction, villous length, and absorptive area of duodenum, jejunum, and ileum compared to control rats. The small intestine of the omeprazole-treated group showed signifcantly higher intraepithelial lymphocytes activation levels compared with the control group. Lower secretory granules of Paneth cells at the base of the crypts were showed in omeprazole-treated rats. They also had signifcantly lower plasma, urinary, bone, and muscle Mg 2+ contents indicating hypomagnesemia with systemic magnesium defciency. In conclusion, prolonged omeprazole treatment-induced small intestinal infammation and villous atrophy, which led to decrease small intestinal magnesium absorption in the condition of proton pump inhibitor-induced hypomagnesemia. Keywords Hypomagnesemia · Infammation · Proton pump inhibitors · Small intestine · Ultrastructure Abbreviations FBG Fast blood glucose IELs Intraepithelial lymphocytes M-to-S Mucosa-to-serosa PPIs Proton pump inhibitors PPIH PPI-induced hypomagnesemia TEER Trans-epithelial electrical resistance TJ Tight junction Introduction Proton pump inhibitors (PPIs) are common and efective medication to treat acid-peptic diseases. PPIs irreversibly bind to H + –K + ATPase pump on the luminal surface of the parietal cell that leads to a suppression of gastric acid secre- tion. Adverse efects of prolonged PPIs administration are gastric mucosal atrophy, enlargement of the parietal and enterochromafn-like cells, and decrease the number of gas- tric chief cells (Masaoka et al. 2008; Tanaka et al. 2019). However, intestinal epithelial cell modality in prolong PPIs administration is not studied. In the adult human, approximately 30 m 2 of the intestinal absorptive area was reported (Helander and Fändriks 2014), signifcant loss of which can lead to malabsorption. Histo- morphologically, the crypt-villus axis in the small intestine is a unique characteristic mucosal feature in explaining the functional structure of the surface lining epithelia (De Gre- gorio et al. 2018). Alteration in villus height, crypt depth, and enterocyte area can be used to estimate intestinal func- tion (Makovicky et al. 2014). The intestinal epithelium consists of multiple functional cell types, i.e., enterocytes, * Narongrit Thongon narongritt@buu.ac.th 1 Division of Anatomy, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, 169 Long-Hard Bangsaen Rd., Saensook, Muang, Chon Buri 20131, Thailand 2 Division of Physiology, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, Chon Buri, Thailand