Microvascular injury during gastric mucosal damage by anti-inflammatory drugs in pigs and rats

Rainsford, K. D.

doi:10.1007/bf02176417

Cited by 56 publications

(24 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, lower dose of indomethacin (25 mg/kg) did not significantly affect the level of MPO in gastric tissues [15]. The enhanced neutrophil infiltration might be attributed to the reported increases in TNF-α and leukotriene synthesis in indomethacin-induced gastric injury [3], and these inflammatory mediators stimulate neutrophil adherence by upregulation of adhesion molecules [4]. In addition, it was reported that NO decreases the adhesive capacity of endothelial cells [5].…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Modulation of indomethacin‐induced gastric injury by spermine and taurine in rats

Motawi

Elgawad

Shahin

2007

J Biochem & Molecular Tox

View full text Add to dashboard Cite

This study investigated the involvement of neutrophil infiltration, nitric oxide (NO) generation, and oxidative stress in indomethacin-induced ulcer and the possible gastroprotective potentials of spermine and taurine, known for their tissue regenerating and antioxidant effects, respectively. Male Wistar albino rats (180-220 g) were allocated into a normal control group, ulcer control group (received a single dose of indomethacin 40 mg-kg p.o.), and two ulcer groups pretreated with spermine (150 mg-kg p.o. 1 h before ulcer induction) and taurine (250 mg-kg i.p. for three consecutive days before ulcer induction). The animals were killed 6 h after indomethacin administration, and the gastric juice, serum, and mucosal tissue were used for gastric injury evaluation. Both modulators significantly ameliorated the indomethacin-induced gastric lesions in glandular mucosa. Notably, spermine exhibited the most pronounced effect as manifested by great reduction in the gastric ulcer index, normalization of the elevated gastric acidity, and triggering of mucin production. Spermine and taurine were able to decrease the elevated levels of gastric myeloperoxidase, conjugated diene, and serum NO. However, the lowered tissue NO content was markedly elevated only by taurine. The antioxidant action of taurine was illustrated by restoration of the depressed content of glutathione, normalization of the inhibited activities of glutathione reductase, and superoxide dismutase. These results suggest that spermine and taurine confer significant gastroprotection against indomethacin-induced gastric injury with the priority of spermine.

show abstract

Section: Discussionmentioning

confidence: 95%

“…This leads to upregulation of tumor necrosis factor-alpha (TNF-α) and increased production of leukotrienes [3]. These inflammatory mediators stimulate the adherence of neutrophils to the vascular endothelium through upregulation of adhesion molecules [4].…”

Section: Introductionmentioning

confidence: 99%

Modulation of indomethacin‐induced gastric injury by spermine and taurine in rats

Motawi

Elgawad

Shahin

2007

J Biochem & Molecular Tox

View full text Add to dashboard Cite

show abstract

“…Therefore, in addition to the enhanced gastric motility, other mechanisms must be also involved in the earliest changes in the gastric mucosal cells after indomethacin treatment. Indeed, Rainsford and Willis (20) and Rainsford (21) reported that indomethacin given p.o. at 5 mg/kg to pigs induced damage of gastric mucosal capillaries within 10 to 15 min and suggested that this capillary damage develops to severe damage to sur rounding tissues.…”

Section: Discussionmentioning

confidence: 99%

16,16-Dimethyl prostaglandin E2 protects gastric mucosal surface epithelial cells from indomethacin-induced damage in rats.

et al. 1987

View full text Add to dashboard Cite

Abstract-The protective effect of 16,16-dimethyl prostaglandin E2 (dmPGE2) against early damage induced by indomethacin in the rat gastric mucosal surface epithelial cells was studied using a scanning electron microscope. Indomethacin (10 or 25 mg/kg, p.o.) induced a widespread exfoliation of the surface epithelial cells and an exposure of the lamina propria both in the corpus and antrum within 1 hr after the administration.Pretreatment with dmPGE2 (0.3, 3 or 30 acg/kg , p.o.) 30 min before indomethacin (25 mg/kg) dose-dependently inhibited these damages.The effects of dmPGE2, at least on the surface epithelial cells in the corpus, appear to be related to the prevention of damage formation itself and is unrelated to the enhancement of reconstitution of once damaged mucosa. Enhanced gastric motility by indomethacin was potently inhibited by pretreatment with 3 and 30 ug/kg of dmPGE2, but not with 0.3 ug/kg. dmPGE2 pretreatment (30 /cg/kg) significantly decreased the absorption of indomethacin (25 mg/kg) when determined 10 min after giving indomethacin, but did not affect it when determined 30 and 60 min later. We conclude that dmPGE2 protects gastric mucosal surface epithelial cells from indomethacin injury at an early stage, partly by inhibiting gastric motility.

show abstract

“…Furthermore, as a regulator of phospholipid metabolism, PLA2 catalyzes the release of free fatty acids and lysophosphatides from cellular mem branes. These free fatty acids, in the form of arachidonic acid, serve as a primary substrate for eicosanoid produc tion yielding prostaglandins, leukotrienes and lipoxins, all o f which have multiple vasoactive and cellular regulatory functions [7,9], The lysophosphatides generated by PLA2 from cellular membranes are potentially cytotoxic and lysophosphatidylcholinc is the precursor of platelet-acti vating factor, which itself has been associated with muco sal injury [10], Micrographs of the gastric mucosa exposed to necrotiz ing agents show edema, vacuolization and necrosis of the luminal epithelial cells [11]: these lesions morphologically resemble those caused by ischemic-reperfusion injury in the intestine [12], Furthermore, there is abundant evi dence that stress-and drug-induced gastrointestinal dam age is associated with mucosal microcirculatory distur bances [13,14]. Recent studies have shown that ischemic insult to intestinal mucosa is accompanied by enhanced generation of oxygen-derived free radicals (ODFR) and increased PLA2 activity [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Effect of Quinacrine, a Phospholipase A<sub>2</sub> Inhibitor on Stress and Chemically Induced Gastroduodenal Ulcers

Moutaery

Tariq²

1997

Digestion

View full text Add to dashboard Cite

Quinacrine, a phospholipase A₂ inhibitor, has been studied for its ability to inhibit gastric secretion and to protect the gastric and duodenal mucosa against chemically and stress-induced ulcers. Acid secretion studies were undertaken in pylorus-ligated rats with and without quinacrine treatment. Experimental gastric lesions were induced by water-immersion restraint stress, indomethacin and 80% ethanol in rats; whereas duodenal ulcers were produced by treatment of rats with cysteamine. The level of nonprotein sulfhydryl compounds and gastric wall mucus were also measured in the glandular stomach of the rats following ethanol-induced gastric lesions. The results of this study demonstrate that quinacrine produces a dose-dependent inhibition of gastric acid secretion in rats. Pretreatment with quinacrine significantly attenuated the formation of stress-, indomethacin- and ethanol-induced gastric lesions. Quinacrine also protected intestinal mucosa against cysteamine-induced duodenal ulcers. The antiulcer activity of quinacrine was associated with appreciable inhibition of ethanol-induced depletion of nonprotein sulfhydryls and gastric wall mucus. These findings point towards the mediation of sulfhydryls in quinacrine-induced gastrointestinal cytoprotection. In conclusion, this study demonstrates that quinacrine possesses significant antiulcer and cytoprotective activity against various experimentally induced gastroduodenal lesions. Although the mechanism of action of quinacrine requires further evaluation, the experimental observations derived from this study may have future clinical relevance and therefore deserve to be investigated thoroughly.

show abstract

Microvascular injury during gastric mucosal damage by anti-inflammatory drugs in pigs and rats

Cited by 56 publications

References 1 publication

Modulation of indomethacin‐induced gastric injury by spermine and taurine in rats

Modulation of indomethacin‐induced gastric injury by spermine and taurine in rats

16,16-Dimethyl prostaglandin E2 protects gastric mucosal surface epithelial cells from indomethacin-induced damage in rats.

Effect of Quinacrine, a Phospholipase A<sub>2</sub> Inhibitor on Stress and Chemically Induced Gastroduodenal Ulcers

Contact Info

Product

Resources

About