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The present study investigated the protective effect of L-citrulline on gastric mucosal injury induced by ischemia- reperfusion (IR) in rats. Under anesthesia, the celiac artery was clamped for 30 min, and then the clamp was removed for 60 min reperfusion. Sixty minutes before ischemia, L-citrulline was administered intragastrically at doses of 300, 600, and 900 mg/kg. After the experiment, the stomachs were removed for biochemical and histological examinations. Pretreatment with L-citrulline (300, 600, and 900 mg/kg) significantly ameliorated the gastric damage caused by IR. Moreover, L- citrulline prevented the production of lipid peroxidation and inhibited the increase of myeloperoxidase activity. The elevation in total nitric oxide synthase (NOS) activity, inducible NOS activity, and inducible NOS protein expression as well as the decrease in constitutive NOS activity and gastric mucus level in the gastric mucosa induced by IR were significantly prevented. However, the protective effect mediated by L-citrulline was significantly antagonized by coadministration of L-nitroarginine methyl ester (10 mg/kg, s.c.). These results suggest that part of the mechanism of gastric protection by L-citrulline might be through inhibiting neutrophil infiltration and preserving gastric mucus synthesis and secretion in rats, functions that are closely related to the maintenance of constitutive NOS activity. Key words: L-citrulline, ischemia-reperfusion, nitric oxide, gastric mucus, neutrophil infiltration, rat. La presente etude a eu pour but d'examiner l'effet protecteur de la L-citrulline sur la lesion de la muqueuse gastrique induite par ischemie-reperfusion (IR) chez des rats. Sous anesthesie, on a pose un clamp sur l'artere coeliaque durant 30 min; apres cette periode, on a retire le clamp pour soumettre l'artere a une reperfusion de 60 min. On a administre la L-citrulline par voie intragastrique en doses de 300, 600 et 900 mg/kg, 60 min avant l'ischemie. Apres l'experience, on a preleve les estomacs et effectuer des analyses biochimiques et histologiques. Le pretraitement a la L-citrulline (300, 600 et 900 mg/kg) a significativement diminue la lesion gastrique causee par IR. De plus, la L-citrulline a prevenu la peroxydation des lipides et l'augmentation de l'activite de la myeloperoxydase. Elle a aussi empeche de facon significative l'elevation de l'activite totale de la NO synthase (NOS), de l'activite de la NOS inductible et de l'expression de la proteine NOS inductible, ainsi que la diminution du taux de mucus et de l' activite de la NOS constitutive dans la muqueuse gastrique. Toutefois, la coadministration de L-nitroarginine ester methylique (10 mg/kg, s.c.) a antagonise de maniere considerable l'effet protecteur vehicule par la L-citrulline. Ces resultats donnent a penser que le mecanisme de protection gastrique par la L-citrulline pourrait impliquer l' inhibition de l' infiltration des neutrophiles et la preservation de la synthese et de la secretion de la muqueuse gastrique, qui sont etroitement associees au maintien de l'activite de constitutive NOS. Mots-cles : L-citrulline, ischemie-reperfusion, monoxyde d'azote, mucus gastrique, infiltration des neutrophiles, rat. [Traduit par la Redaction], Introduction Gastric ischemia-reperfusion (IR) injury is a significant problem in numerous situations such as trauma, major surgery, and nonsteroidal anti-inflammatory drug administration (Kitahora and Guth 1987; Villegas et al. 2004). [...]