Oxygen Free Radicals and Lipid Peroxidation in the Pathogenesis of Gastric Mucosal Lesions Induced by Indomethacin in Rats

Abstract

The relationship of gastric hypermotility to mucosal hemodynamics, lipid peroxidation and vascular permeability changes was investigated in the pathogenesis of indomethacin-induced gastric lesions in rats. Subcutaneous administration of indomethacin (25 mg/kg) produced an increase in both the amplitude and frequency of stomach contraction from 30 min after treatment, resulting in hemorrhagic damage 2 h later. Gastric mucosal blood flow measured by a Laser flowmetry showed oscillatory fluctuations under hypercontractile states: a decrease during contraction followed by an increase during relaxation. Mucosal lipid peroxidation and vascular permeability were significantly increased with time after indomethacin treatment, and these changes preceded the appearance of hemorrhagic damage. All these events were prevented when gastric hypermotility was inhibited by atropine or 16,16-dimethyl prostaglandin E₂. Pretreatment of the animals with allopurinol and hydroxyurea or continuous infusion of superoxide dismutase and dimethyl sulfoxide during a test period also attenuated these functional changes and mucosal lesions induced by indomethacin, without affecting the motility response. We conclude that oxygen free radicals may play a role in the development of mucosal lesions associated with gastric hypermotility in indomethacin-treated rats.

Mechanisms by which endogenous glucocorticoid protects against indomethacin-induced gastric injury in rats

“…This idea was supported by the present findings that the microvascular permeability was markedly increased in adrenalectomized rats, irrespective of whether or not they were given indomethacin, and that this alteration was totally inhibited by supplementations of corticosterone. Previous studies (39) suggested that the increase of gastric microvascular permeability in indomethacin-treated rats is caused by vascular disturbances due to abnormal contraction of the stomach wall mediated by several events, including neutrophil-endothelial interaction. It is assumed that the effect of corticosterone on the microvascular permeability is brought about by its inhibitory action on gastric hypermotility induced by indomethacin through amelioration of glucose metabolism.…”

“…Indeed, indomethacin shows potent ulcerogenic action in experimental animals (38,44). The mechanism by which indomethacin induces gastric injury is generally considered to involve depletion of PGs, yet it has proven more complicated than expected and involves multiple, closely interacting elements such as gastric hypermotility, microcirculatory disturbances, neutrophil-endothelial cell interactions, and superoxide radicals, in addition to PG deficiency (39,44).…”

Protective effect of salusin-α and salusin-β against ethanol-induced gastric ulcer in rats

“…The neutrophil infiltration in gastric mucosa induced by ethanol has been shown to be closely related to the formation of lesions [10]. Determination of myeloperoxidase (MPO) activities, which are deemed as the main marker of neutrophil infiltration, is one of the main indicators of gastric injuries [11]. The invasion of stomach tissues marked by neutrophils with increased MPO activity causes gastric mucosa injury [12].…”

Reactive Oxygen Species in the Pathogenesis of Stress-Induced Gastric Ulceration in Rats and Protective Effect of Omeprazole

“…Various mechanisms like decreased gastric mucosal blood flow (K ita g a w a et al. 1979), increased gastric motility ( Gar ric k et al 1986), acetylcholine as a mediator of vagal hyperactivity (G a ton et al 1993), decreased prostaglandin serum (M i II e r 1987) or mucosa level (G it lin et al 1988), and increased vascular permeability (Takeuchi et al 1991) are supposed to be involved in ulcer development. Recently, attention has been focused on the role of reactive oxygen species (ROS).…”

“…ROS have been found to play a role in experimental gastric damage induced by immobilization (M a n c in ell i et al. 1990), hemorrhagic shock ( Ito hand Gut h, 1985), reperfusion (P err y et al 1986), and nonsteroidal antiinflammatory drugs ~Takeuchi et al 1991). It is assumed that the gastric damage in rats induced by Immobilization stress may have a pathogenic mechanism in common with other types ?f stress.…”