The potential therapeutic effect of nitric oxide modulators in experimentally-induced gastric ulcers

Nitric oxide (NO) appears to play a critical role in modulating gastric mucosal defense. Administration of NO donors has been reported to protect the gastrointestinal mucosa against damage induced by several irritants. However, the possible role of NO in healing existing ulcers must be clarified further. Therefore, the present study was designed to assess the effect of modulation of NO on the healing of an indomethacin-induced peptic ulcer using a NO precursor, L-arginine, and a competitive inhibitor of NO synthase, L-NAME. Results of administering L-arginine were compared to those using nitroglycerin (NTG), an NO donor. Rats were injected with a single oral dose of indomethacin (30 mg/kg) and then treated with L-arginine (200 mg/kg, i.p.), NTG (1 mg/kg, i.p.) or L-NAME (15 mg/kg, i.p.) once daily for 7 d starting 4 h after the indomethacin injection. Gross lesion examination and histological assessment were done. NO, prostaglandin (PGE2), and mucin content in gastric tissue were detected. In addition, oxidative stress markers including glutathione (GSH) and lipid peroxides were measured. L-arginine and NTG almost completely healed indomethacin-induced ulceration as indicated by macroscopic and histological examination, restoration of normal levels of NO and GSH, and a significant attenuation of the increase in PGE2 and lipid peroxides induced by indomethacin. In contrast, L-NAME was found to exacerbate mucosal damage. In conclusion, the present study provides further evidence for the role of NO in gastric ulcer healing and it suggests an alternative path to treating the universal problem of non-steroidal anti-inflammatory-drug-induced gastropathy.