MORPHOLOGIC AND MORPHOMETRIC ANALYSIS OF CELLULAR AND SUBCELLULAR STRUCTURES OF RAT GASTRIC MUCOSA AFTER ADMINISTRATION OF E3810, A NOVEL PROTON PUMP INHIBITOR

• Published in: Journal of Toxicologic Pathology Vol. 9; no. 2; pp. 121 - 130
• Main Authors: Aoki, Toyohiko, Fukuta, Taneo, Hosokawa, Satoru, Motooka, Satoru, Nakanowatari, Junichi, Sagami, Fumio, Furuhashi, Masako, Nakahara, Akira, Fukutomi, Hisayuki, Uchiyama, Yasuo
• Format: Journal Article
• Language: English
• Published: Tokyo JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY 1996; The Japanese Society of Toxicologic Pathology; Japan Science and Technology Agency
• Subjects: E3810; ECL cell; Gastrin; Morphometry; Proton pump inhibitor
• ISSN: 0914-9198; 1881-915X; 1347-7404
• DOI: 10.1293/tox.9.121

To further understand gastric mucosal alterations caused by E3810, anovel proton pump inhibitor, in parietal cells, morphometry was applied to gastric tissue of rats administered E3810 subcutaneously at doses of 5, 10, and 20 mg/kg/day for 2 or 5 weeks. Plasma gastrin levels in the 2-week treatment groups were significantly elevated at all doses of E3810, whereas in the 5-week treatment groups, a significant increase in the level was found in rats administered 20mg/kg E3810 only. By light microscopy, the fundic mucosal thickness dose-dependently increased in the 5-week treatment groups. The number of chromogranin-immunopositive enterochromaffin-like (ECL) cells also increased at the dose of 20mg/kgin the 2-week treatment groups and at all doses in the 5-week treatment groups. By electron microscopy of parietal cells, no distinct vacuolization appeared in parietal cells even in rats administered 20mg/kg E3810 for 5 weeks. Morphometrically, the volume and surface density of tubulovesicles did not change in both the 2- and 5-week treatment groups, whereas those of microvilli on secretory canaliculi significantly decreased in the 5-week treatment groups. These results suggest that the increases in mucosal thickness and number of ECL cells after treatment with E3810 are due to hypergastrinemia induced by its prolonged pharmacological effects. Moreover, the changes in morphometric parameters of microvilli on secretory canaliculi in parietal cells may result from the inhibitory effect of E3810 on H+/K+-ATPase. However, the morphologic and morphometric changes in parietal cells after E3810 treatment were slight, compared with those reported previously for omeprazole at the same dose levels.