Rapid Apoptotic Changes in the Gastric Glandular Epithelium of Rats Administered Intraperitoneally with Fusarenon-X.

Abstract

Fusarenon-X (FX) 1.5 mg/kg was administered intraperitoneally (i.p.) to 6-week-old male Wistar rats for examination of pathologic effects on the glandular stomach. Rats ip-treated with sterilized physiological saline were used as control. FX-administered rats showed dilatation of the stomach with increased fluid contents after 1-4 hr. Light microscopically, a few apoptotic karyopyknosis were seen in chief cells in the basal region at 1 hr postadministration (PA) and mitotic inhibition was evident after 2 hr PA. Marked apoptosis of nuclear pyknosis and cytoplasmic inclusions in both zymogenic and oxyntic cells developed from basal to middle regions of the gastric mucous membrane at 2-4 hr PA with a peak at 3 hr. Apoptotic changes of differentiating neck cells and surface epithelia were less evident. Electron microscopy revealed that the chief cells were the main target of FX-induced apoptotosis. The parietal cells were secondarily involved because they phagocytosed chief cell-derived apoptotic bodies. In situ detection of DNA breaks by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) reaction revealed the positive nuclei after 1 hr PA, which increased with time and reached a peak at 3 hr PA, in accordance with apoptotic changes in histological study. Agarose gel electrophoresis of DNA isolated from the gastric mucosae of FX-administered rats showed ladder pattern of DNA fragments after 1.5 hr PA with the maximum distinctness at 3 hr PA.