Ultrastructure of ECL cells in Mastomys after long-term treatment with H2 receptor antagonist loxtidine

Abstract

Gastric ECL-cell hyperplasia and carcinoids (ECLoma) develop after 1 year in rats treated with omeprazole or 2 months in Mastomys treated with loxtidine. The aim of this study was to examine the ultrastructure of ECL cells in Mastomys after loxtidine treatment with an attempt to evaluate whether an impairment of autophagy was involved in the tumorigenesis. Mastomys were given loxtidine for 8 or 27 weeks. Morphological analysis of ECL cells showed that (1) cell size was not increased after 8 or 27 weeks; (2) secretory vesicles, a hallmark feature of welldifferentiated ECL cells, were unchanged after 8 weeks but reduced after 27 weeks; (3) granules were reduced after 8 or 27 weeks; (4) microvesicles were unchanged after the treatment; and (5) vacuoles and lipofuscin bodies were found occasionally after 8 weeks but not at 27 weeks. In addition, the appearance of ECL-cell ultrastructure differed between loxtidine-treated Mastomys and rats treated with omeprazole or subjected to antrectomy, but was similar between Mastomys treated with loxtidine for 27 weeks and mice deficient in CCK(2) receptor. We suggest that the ultrastructure of ECL cells in Mastomys after long-term treatment with loxtidine displayed an impaired formation of vacuoles and lipofuscin bodies, markers of the autophagic pathway.

Pathophysiology of Gastric NETs: Role of Gastrin and Menin

“…Its export from the nucleus de-represses cell cycle progression, leading to uncontrolled proliferation and hyperplasia. It has been observed that hypergastrinemia induced by acid suppression from omeprazole or loxtidine an irreversible H2 receptor antagonist can lead to ECL cell tumors in rodents (28, 38, 39). Indeed, reports are emerging that fundic gland polyps and ECL hyperplasia do arise with prolonged PPI use, but the clinical impact remains uncertain (40–42).…”