Gastric lesions induced by indomethacin (20 mg.kg'1 i.p.) were studied in rats after a 24 hour fast. The size of the lesions was correlated with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v administration) and with the rate of gastric emptying (determined from the phenol red concentration after its intragastric application). These changes were correlated with the prevention of gastric lesions by allopurinol (50 mg.kg'1) after a single dose or once daily for 3 days before indomethacin and by a single dose (15 000 dkg'1) of superoxide dismutase (SOD). Indomethacin significantly increases the rate of gastric emptying concomitantly with gastric vascular permeability. The pretreatment of animals with allopurinol and SOD inhibits gastric lesions as well as gastric vascular permeability without changing gastric emptying which was increased after indomethacin administration. The inhibition of gastric lesion formation and gastric vascular permeability was more marked in rats pretreated with allopurinol for 3 days when compared with rats treated with a single dose of allopurinol only. These results support the suggestion that oxygen-derived free radicals contribute to the pathogenesis of indomethacin-induced gastric lesions.
Pentoxifylline pretreatment protects rat gastric mucosa against indomethacin-induced damage. Lipid peroxidation after indomethacin treatment (determined as thiobarbituric acid reactants) was significantly reduced by a single dose of pentoxifylline. The same was true for pentoxifylline administration for 6 days. There is a relationship between reduced lipid peroxidation, decreased number of circulating activated neutrophils and diminished disposition for acute gastric mucosal lesions induced by indomethacin in pentoxifylline-pretreated rats.