Ammonia aggravates stress-induced gastric mucosal oxidative injury through the cancellation of cytoprotective heat shock protein 70

The relationship between Helicobacter pylori colonization and the formation of stress-induced gastric mucosal injury remains unknown. Since ammonia (NH3) is known as one of the injurious factors in H. pylori-colonized gastric mucosa, the present study is designed to investigate the level of stress-induced gastric mucosal oxidative injury with or without intragastric NH3 overloading. To apply emotional stress, the communication box paradigm was used in the mouse model. Mice (C57BL/6, male) were pretreated with distilled water (responder-H2O) or 0.01% NH3 (responder-NH3) through a gastric tube once a day for a week. Emotional stress was then applied to the responder mice for 3 h per day for 3 d by watching and hearing the behavior of the sender mice subjected to electric shocks to the feet (2 mA, 10 s, 50 s interval). After the communication box protocol, the tissue MPO activity, the contents of TBA-reactive substances (TBARS), and the level of gastric mucosal HSP70 were examined. Responder-NH3 mice developed more severe gastric lesions than the responder-H2O subjects. MPO activity and TBARS contents were enhanced significantly in the responder-NH3 group compared with the responder-H2O subjects. Although the contents of HSP70 in the gastric mucosa increased in the responder-H2O group compared with the control-H2O animals, they were significantly attenuated in the responder-NH3 mice. Excess intragastric NH3 was able to enhance the formation of emotional stress-induced gastric mucosal lesions. This injury may be associated with the enhanced production of oxygen free radicals from accumulated neutrophils under the NH3-mediated cancellation of gastric mucosal cytoprotective HSP70.