Acute parietal and chief cell changes induced by a lethal dose of lipopolysaccharide in mouse stomach before thrombus formation.
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.
Ito
K
K
Safety Research Laboratories, Yamanouchi Pharmaceutical Co Ltd, Tokyo, Japan. itou@yamanouchi.co.jp
Ishida
K
K
Shishido
T
T
Tabata
H
H
Miura
H
H
Okamiya
H
H
Hanada
T
T
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001772:Blood Cell Count / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D019872:Chief Cells, Gastric / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D003594:Cytoplasmic Granules / Q000737:chemistry; D004926:Escherichia coli; D005260:Female; D017506:H(+)-K(+)-Exchanging ATPase / Q000032:analysis; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D010295:Parietal Cells, Gastric / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D010434:Pepsin A / Q000032:analysis; D013927:Thrombosis / Q000139:chemically induced* / Q000473:pathology
D008070:Lipopolysaccharides; D010434:Pepsin A; D017506:H(+)-K(+)-Exchanging ATPase