Effects of ammonia solution on the gastric mucosa in cirrhotic rats and therapeutic effects of geranylgeranylacetone

BACKGROUND: We designed an animal model in order to clarify whether Helicobacter pylori infection causes the gastric mucosal lesion frequently seen in cirrhotic patients. METHODS: Ammonia (NH3) solution was given to rats with carbon tetrachloride-induced cirrhosis. The gastric mucosal hexosamine (Hx) content and histopathological findings in the cirrhotic rats were analysed and compared with those of the intact liver rats. Moreover, the usefulness of geranylgeranylacetone (GGA) was investigated in both rat groups. Both rat groups were subdivided according to the treatment as follows: a control group, an NH3 (0.02% solution) group, and an NH3 + GGA (400 mg/kg per day) group; and fed for 4 weeks. RESULTS: The gastric mucosal Hx content of the control group of the cirrhotic rats (16.7 +/- 5.2 microg/mg) was significantly lower than that of the control group of the intact liver rats (26.6 +/- 4.5 microg/mg, P < 0.05). In the cirrhotic rats, the Hx content of both the NH3 (31.9 +/- 13.1 microg/mg) and the NH3 + GGA group (31.9 +/- 9.8 microg/mg) was significantly higher than the Hx content of the control group (P < 0.05). Microscopically, in the cirrhotic rats, while scattered mucosal erosions were recognized in three of five rats of the NH3 group, there were no erosions in any rats of the NH3 + GGA group. CONCLUSIONS: These data suggest that the gastric mucosal defence mechanism is defective in liver cirrhosis and that NH3 enhances this defensive mechanism by acting as mild irritant; however, in some cirrhotics this results in gastric erosion due to excessive irritation. Geranylgeranylacetone protects the gastric mucosa against NH3 irritation in cirrhotics without enhancing the Hx content. Thus, H. pylori infection may be a possible cause of the gastric mucosal lesion in patients with liver cirrhosis. The mechanism of the therapeutic effect of GGA is not due to an enhancement of the gastric mucosal Hx content.