Formation Of Gastric Mucosal Injury Research Articles

Gastroprotective activity of Eriobotrya japonica seed extract on experimentally induced gastric lesions in rats

The effect of Eriobotrya japonica seed extract (ESE) prepared with 70% ethanol on gastric mucosal injury was investigated. Six experimental models with different action mechanisms were used for the evaluation. Three concentrations of ESE were prepared for each model. ESE administration was initiated 14 days before induction of gastric mucosal injury, and its effect was investigated. ESE inhibited formation of gastric mucosal injury.

Prostaglandin/Cyclooxygenase Pathway in Ghrelin-Induced Gastroprotection against Ischemia-Reperfusion Injury

Ghrelin is involved in the control of food intake, but its role in gastroprotection against the formation of gastric mucosal injury has been little elucidated. We studied the effects of peripheral (i.p.) and central (i.c.v.) administration of ghrelin on gastric secretion and gastric mucosal lesions induced by 3 h of ischemia/reperfusion (I/R) with or without inhibition of ghrelin growth hormone secretagogue type 1a receptor (GHS-R1a) by using ghrelin antagonist, d-Lys(3)-GHRP-6; blockade of cyclooxygenase (COX)-1 (indomethacin, SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole]) and COX-2 (rofecoxib); and bilateral vagotomy or capsaicin denervation. I/R produced typical gastric erosions, a significant fall in the gastric blood flow (GBF), an increase in gastric myeloperoxidase (MPO) activity and malonyldialdehyde (MDA) content, and the up-regulation of mucosal ghrelin mRNA. Ghrelin dose-dependently increased gastric acid secretion and significantly reduced I/R-induced gastric erosions, while producing a significant rise in the GBF and mucosal PGE(2) generation and a significant fall in MPO activity and MDA content. The protective and hyperemic activities of ghrelin were significantly attenuated in rats pretreated with d-Lys(3)-GHRP-6 and capsaicin denervation and completely abolished by vagotomy. Indomethacin, SC560, and rofecoxib, selective COX-1 and COX-2 inhibitors, attenuated ghrelin-induced protection that was restored by supplying the methyl analog of prostaglandin (PG) E(2). The expression of mRNA for COX-1 was unaffected by ghrelin, but COX-2 mRNA and COX-2 protein were detectable in I/R injured mucosa and further up-regulated by exogenous ghrelin. We conclude that ghrelin exhibits gastroprotective and hyperemic activities against I/R-induced erosions, the effects that are mediated by hormone activation of GHS-R1a receptors, COX-PG system, and vagal-sensory nerves.

Rat gastric mucosal cells express ICAM-1 and proinflammatory cytokines during indomethacininduced mucosal injury

Adhesion molecules and cytokines are known to be involved in the formation of acute gastric mucosal injury. However, it is not clear whether the gastric mucosal cells express these molecules and modulate the inflammation. To clarify whether gastric mucosal cells express intercellular adhesion molecule-1 (ICAM-1) and proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1-α (IL-1α), and cytokine-induced neutrophil chemoattractant-2-β (CINC-2β)) in the formation of gastric mucosal injury, we have used rat indomethacin-induced gastric mucosal lesions as an in vivo model. The gene expression of all cytokines and ICAM-1 increases at the early stages of indomethacin-induced gastritis (TNF-α and IL-1-α gene expression began to increase earlier than that of ICAM-1 and CINC-2-β) and can mainly be detected in the gastric epithelial layer. To further identify the source of those molecules, the epithelial cells were separated into seven fractions according to their sizes by a counterflow elution. ICAM-1 and CINC-2-β gene expressions are particularly enhanced in the middle-sized cell fractions that are rich in gastric mucous-producing cells. The effect of TNF-α or IL-1-α on the gene expression of ICAM-1 and cytokines was examined by using RGM-1 cells as a model for gastric mucosal cells. RGM-1 cells show an augmented ICAM-1 and proinflammatory cytokine expression in response to TNF-α or IL-1-α stimulation. Moreover, immunohistochemical staining also reveals an increase in ICAM-1 and CINC protein production in RGM-1 cells in response to TNF-α stimulation. We conclude that gastric mucosal cells express various cytokines and an adhesion molecule during the formation of acute gastric mucosal injury and that they may modulate the inflammation.

Intracisternal injection of basic fibroblast growth factor reduces the severity of gastric mucosal lesions evoked by ethanol in rats.

This study was conducted to examine the hypothesis that basic fibroblast growth factor (bFGF) may have an anti-ulcer action through an acid-independent mechanism. The intracisternal injection of bFGF (1 microgram/10 microliters) significantly attenuated the development of gastric mucosal damage evoked by either subcutaneous indomethacin or intragastric absolute ethanol. On the other hand, intraperitoneally injected bFGF (1 microgram) failed to inhibit the formation of gastric mucosal injury by indomethacin or ethanol. These results suggest that bFGF acts in the brain to exert a gastroprotective action. Since ethanol-induced gastric lesion formation does not depend upon luminal acid, we speculate that an acid-independent mechanism may mediate the anti-ulcer action of central bFGF.

Role of oxygen radicals in the pathogenesis of gastric mucosal lesions induced by water-immersion restraint stress and burn stress in rats.

The formation of gastric mucosal lesions and the increase in thiobarbituric acid (TBA)-reactive substances induced by water-immersion restraint stress or burn stress in rats were significantly inhibited by the treatment with superoxide dismutase (SOD) and/or catalase. Allopurinol inhibited the formation of gastric mucosal injury induced by burn stress, but not the increase in TBA reactants. A drop in the polymorphonuclear leukocyte (PMN) count induced by an injection of anti-rat PMN antibody did not inhibit the aggravation of gastric mucosal lesions or the increase in TBA reactants in either of the stress models. These results suggest that active oxygen species and lipid peroxidation may play a role in the formation of gastric mucosal damage induced by stress. Reduced microcirculation of the gastric mucosa induced by water-immersion restraint or burn stress did not change following treatment with SOD and/or catalase, suggesting that the effectiveness of SOD and catalase on the gastric mucosal lesions induced by stress may occur via the scavenging of oxygen radicals, and not through an effect on gastric mucosal microcirculation.

Role of PAF for the formation of gastric mucosal injury induced by ischemia-reinfusion in the rat

Role of PAF for the formation of gastric mucosal injury induced by ischemia-reinfusion in the rat

Role of oxygen-derived free radicals in gastric mucosal injury induced by ischemia or ischemia-reperfusion in rats.

Oxygen-derived free radicals have been implicated as possible mediators in the development of tissue injury induced by ischemia and reperfusion. Clamping of the celiac artery in rats reduced the gastric mucosal blood flow to 10% of that measured before the clamping. The area of gastric erosions and thiobarbituric acid (TBA) reactants in gastric mucosa were significantly increased 60 and 90 min after clamping. These changes were inhibited by treatment with SOD and catalase. Thirty and 60 min after reoxygenation. produced by removal of the clamps following 30 min of ischemia, gastric mucosal injury and the increase in TBA reactants were markedly aggravated compared with those induced by ischemia alone. SOD and catalase significantly inhibited these changes. The serum alpha-tocopherol/cholesterol ratio, an index of in vivo lipid peroxidation, was significantly decreased after long periods of ischemia (60 and 90 min), or after 30 and 60 min of reperfusion following 30 min of ischemia. These results indicated that active oxygen species and lipid peroxidation may play a role in the pathogenesis of gastric mucosal injury induced by both ischemia alone and ischemia-reperfusion. Although, allopurinol inhibited the formation of gastric mucosal injury and the increase in TBA reactants in gastric mucosa, the depletion of polymorphonuclear leukocytes (PMN) counts induced by an injection of anti-rat PMN antibody did not inhibit these changes. As compared with the hypoxanthine-xanthine oxidase system. PMN seem to play a relatively small part in the formation of gastric mucosal injury induced by ischemia-reperfusion.

Roles of gastric motility changes in cytoprotection induced by acetazolamide and cysteamine in rats.

The present study was undertaken using acetazolamide (AZ) and cysteamine (Cys) to investigate the relationship between gastric motor activity and the phenomenon of "cytoprotection" in rats. Both AZ (10-100 mg/kg) and Cys (10-100 mg/kg), given either p.o. or s.c., significantly reduced the formation of gastric mucosal injury caused by HCl-ethanol (1 ml of 60% ethanol in 150 mM HCl, p.o.). The protective effect of Cys appeared within 10 min, reached the maximal levels 30 min later, while that of AZ appeared from 30 min after administration and became potent with a latency period after treatment. Neither indomethacin (IM: 5 mg/kg, s.c.) nor N-ethylmaleimide (NEM: 5 mg/kg, s.c.) significantly affected the protective effect of Cys, whereas that of AZ was almost totally antagonized by IM. Both AZ and Cys, given either intragastrically or s.c., significantly inhibited gastric motor activity measured as intraluminal pressure recordings, but had minimal effect on acid and alkaline secretion. IM significantly attenuated the inhibitory effect of AZ on the motor activity, while NEM did not affect the inhibited motor responses caused by AZ and Cys. A significant relationship was found between the inhibitory effects of these two drugs on gastric motor activity and HCl-ethanol-induced mucosal injury, the correlation coefficient being 0.819 (P less than 0.01). When the mucosal folds were visualized with Gentian Violet (1 ml of 0.5% v/v, p.o.), both AZ and Cys significantly prevented the localized staining along the mucosal folds, suggesting dissolution of the folds. These results suggest that both AZ and Cys protect the gastric mucosa against injury caused by HCl-ethanol, probably through a dissolution of mucosal folds due to inhibition of gastric motor activity.