Gastro-protective effect of l-arginine against nitric oxide deficiency-related mucosal injury induced by indomethacin: Does age matter?

Gastric ulcer is a common disease with increased prevalence in the aged population. Aged gastric mucosa has increased susceptibility to injury along with nonsteroidal anti-inflammatory drugs use due to impaired mucosal defense and decreased vasodilator release. We investigated whether l-arginine could protect against age-related gastric ulceration induced by indomethacin. Aged and adult male Wistar rats were administered sole and combined treatment of  l-arginine and N ω -nitro-l-arginine methyl ester ( l-NAME) before induction of gastric ulceration by indomethacin. The gastroprotective effect of  l-arginine was displayed only in adult rats with indomethacin-induced gastric ulceration, as evidenced by a significant decrease in ulcer index, oxidative stress parameters, and mucosal myeloperoxidase activity along with increased mucosal PGE2 levels. Interestingly, the mucosal gene expressions of NF-кB, iNOS, and COX-2 were significantly suppressed by  l-arginine pretreatment and aggregated upon pretreatment with  l-NAME in both adult and aged rats treated with indomethacin. In conclusion,  l-arginine protected the rats' gastric mucosa against indomethacin-induced gastric ulceration, possibly, at least in part, by enhancement of mucosal nitric oxide/PGE2 content along with suppressing gastric inflammation and oxidative stress. This study supposed that the gastroprotective effect of  l-arginine depends on aging, and even so, the adoption of a new approach to gastric ulcer treatment for the aged population is warranted.