Gastric damage and body weight loss in LHA-lesioned rats: effects of cytoprotective geranylgeranylacetone.

Abstract

We investigated the development of gastric damage and body weight (BW) loss in lateral hypothalamic area (LHA)-lesioned rats, measured 2 h and 1 and 3 days after the lesioning (experiment 1), as well as the effects of geranylgeranylacetone (GGA), a cytoprotective antiulcer agent, on these disorders (experiment 2). In experiment 1, BW of LHA-lesioned rats decreased throughout the 3-day experiment. In LHA-lesioned rats, gastric mucosal lesions appeared 1 day after lesioning in the glandular portion and persisted, whereas those in the rumenal portion appeared only after 3 days. Gastric transepithelial potential differences (PDs) of glandular portion began to decrease after 2 h and had decreased in both portions. Gastric acid output was increased transiently at 2 h but it was not high after 1 day and after 3 days was lower than that in sham-LHA-lesioned rats. In experiment 2, PDs of the rumenal decreased more in LHA-lesioned rats than in sham-LHA-lesioned rats pair fed to LHA-lesioned rats after 3 days. Three days of treatment with GGA (200 mg/kg ip) improved PDs of rumenal and glandular portions in LHA-lesioned rats and reduced lesions of the rumenal portion. Loss of BW in LHA-lesioned rats was significantly but not completely inhibited by GGA. These results indicate that disturbance to the gastric defensive mechanism plays an important role in the development of gastric lesions after LHA lesions and that the impairment of gastric functions may be a partial cause of the loss of BW in LHA-lesioned rats.