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Studies on gastric mucosal cell injury induced by Helicobacter pylori
S Mitani-Ehara1, M Asaka, M Katagiri
1Third Department of Internal Medicine, School of Medicine, University of Hokkaido, Sapporo, Japan.
Abstract:
The cause of gastric cell injury induced by Helicobacter pylori was investigated in vitro using gastric mucosal cells derived from male Japanese white rabbits. To evaluate the contribution of the potent urease activity of H. pylori to gastric mucosal cell injury, the supernatant of the H. pylori bacterial pellet, solubilized with N-octyl-glucoside, was added to the gastric mucosal cell suspension. Cell injury was assessed by lactate dehydrogenase (LDH) release into the extracellular fluid. Treatment of cells with H. pylori extracts together with urea resulted in high levels of LDH release, suggesting definite gastric mucosal cell injury, and elevation of ammonia concentration was also observed. In contrast, incubation with H. pylori extracts alone or urea solution alone did not result in increased LDH release or elevated ammonia concentrations. The degree of LDH release from gastric mucosal cells due to H. pylori extracts in the presence of urea was similar to that induced by administration of the same amount of exogenous ammonia. The addition of acetohydroxamic acid, a potent specific urease inhibitor, remarkably inhibited ammonia production, the elevation of pH of extracellular fluid, and LDH release in a dose-dependent manner. These results suggest that ammonia produced by potent urease activity of H. pylori in the presence of urea plays an important role in the pathogenesis of gastric mucosal cell injury.
Insights
Helicobacter pylori urease activity, in the presence of urea, generates ammonia that causes gastric mucosal cell injury. A urease inhibitor blocked this ammonia production and injury, confirming its role in pathogenesis.
Area of Science:
- Gastroenterology
- Microbiology
- Cell Biology
Background:
- Helicobacter pylori is a major cause of gastric diseases.
- The urease enzyme of H. pylori is crucial for its survival in the stomach.
- The precise mechanism of H. pylori-induced gastric cell injury requires further elucidation.
Purpose of the Study:
- To investigate the role of H. pylori urease activity in gastric mucosal cell injury in vitro.
- To determine if ammonia produced by H. pylori contributes to gastric cell damage.
Main Methods:
- Gastric mucosal cells from rabbits were incubated with H. pylori extracts and urea.
- Cell injury was quantified by measuring lactate dehydrogenase (LDH) release.
- Ammonia production and extracellular pH were monitored.
- The effect of a urease inhibitor, acetohydroxamic acid, was assessed.
Main Results:
- H. pylori extracts plus urea caused significant gastric mucosal cell injury (LDH release) and ammonia production.
- H. pylori extracts or urea alone did not induce significant injury.
- Ammonia production and cell injury were dose-dependently inhibited by acetohydroxamic acid.
- Exogenous ammonia mimicked the cell injury caused by H. pylori extracts with urea.
Conclusions:
- The potent urease activity of H. pylori, producing ammonia in the presence of urea, plays a significant role in gastric mucosal cell injury.
- Ammonia is a key mediator in the pathogenesis of H. pylori-induced gastric damage.