Relation between intestinal iNOS activation, epithelial cell viability and vascular leakage following Helicobacter pylori endotoxin challenge

Introduction: The infection with Helicobacter pylori leads to gastroduodenal mucosal injury. Less is known on the mechanism of action of its lypopolysaccharide component (LPS). Nitric oxide generated in large amounts by the inducible nitric oxide synthase (iNOS) following LPS or/and cytokine exposure plays a key role in inflammation.

Aim: We examined the relation between iNOS activation, inflammation and epithelial cell viability of intestinal tissues following Helicobacter pylori LPS challenge in vivo in male Wistar rats.

Methods and results: We found that administration of Helicobacter pylori LPS (3mg/kg, iv.) caused the reduction in duodenal epithelial cell viability (by 60±6 and 52±8% as assessed by the MTT conversion and trypan blue exclusion tests, respectively; n=9–10; p<0.05), the increase in vascular permeability (assessed by the albumin leakage technique) and the activation of iNOS (assessed by the citrulline assay) over 5 hours in the duodenum and jejunum. Concurrent administration of the selective iNOS inhibitor, 1400W (0.2–1mg/kg, sc.) with Helicobacter pylori LPS reversed the activation of iNOS (1mg/kg dose), dose-dependently decreased vascular albumin leakage (by a maximum of 85±4 and 92±5% in the duodenum and jejunum, respectively, n=6, p<0.01) and abolished (1mg/kg dose) the Helicobacter pylori LPS-induced decrease in duodenal epithelial cell viability.

Conclusion: Helicobacter pylori LPS is capable to activating iNOS in intestinal tissues. The overproduction of nitric oxide by Helicobacter pylori LPS-activated iNOS seems cytotoxic, and causes the reduction of the viability of epithelial cells and the increase in vascular permeability.