Toxicologic Pathology

 

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Toxicologic Pathology, Vol. 28, No. 2, 304-309 (2000)
DOI: 10.1177/019262330002800210

Acute Parietal and Chief Cell Changes Induced by a Lethal Dose of Lipopolysaccharide in Mouse Stomach before Thrombus Formation

Kyoko Ito

Safety Research Laboratories, Yamanouchi Pharmaceutical Co Ltd, Tokyo, Japan,

Katsuhiko Ishida

Safety Research Laboratories, Yamanouchi Pharmaceutical Co Ltd, Tokyo, Japan

Takao Shishido

Safety Research Laboratories, Yamanouchi Pharmaceutical Co Ltd, Tokyo, Japan

Hajime Tabata

Safety Research Laboratories, Yamanouchi Pharmaceutical Co Ltd, Tokyo, Japan

Hisaki Miura

Safety Research Laboratories, Yamanouchi Pharmaceutical Co Ltd, Tokyo, Japan

Hideaki Okamiya

Safety Research Laboratories, Yamanouchi Pharmaceutical Co Ltd, Tokyo, Japan

Takanori Hanada

Safety Research Laboratories, Yamanouchi Pharmaceutical Co Ltd, Tokyo, Japan

The common lipopolysaccharide (LPS)-induced gastric lesions, such as erosions or ulcers, have been investigated in depth. Little is known, however, about the acute gastric lesions following a high dose of LPS. In a time-course study, ICR female mice were given a high subcutaneous dose of LPS (50 mg/kg). Mice were sacrificed at 4, 6, 12, and 24 hours after dosing and were assessed histopathologically for acute gastric lesions. The major gastric changes were seen in the fundic region and included vacuolar degeneration of parietal cells and apoptosis of chief cells. The vacuole in parietal cells was apparent as early as 4 hours postinjection (PI), and apoptosis of chief cells was apparent at 12 hours PI. Thrombus formation, in contrast, was not seen until 24 hours PI. No erosion, ulcer, or hemorrhage was seen in any gastric region in any of the treated animals at 24 hours PI. These results indicate that a subcutaneous high dose of LPS in mice causes vacuolar degeneration of parietal cells and apoptosis of chief cells before thrombus formation or subsequent ulcerative lesions.

Key Words: Lipopolysaccharide • gastric mucosa • acute • mice • vacuolation • parietal cell • apoptosis • chief cell


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