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

Abstract

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 Nω‐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.