Inhibitory effect of non-steroidal anti-inflammatory drugs on mucosal cell proliferation associated with gastric ulcer healing

Levi, S; Walport, Mark J.; Hodgson, H. J. F.; Goodlad, R A; Lee, C.Y; Stamp, Gordon; Wright, Nicholas A.

doi:10.1016/0140-6736(90)92341-e

Cited by 173 publications

(87 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1, 2 Indeed, prostaglandins have been shown to be important mediators of epithelial restitution in the stomach, 28,29 and their importance in repair of ulcers is underscored by the marked ability of NSAIDs to interfere with this process. 30,31 While it is now clear that there are at least two isoforms of cyclooxygenase (the principle enzyme responsible for prostaglandin synthesis), the relative contribution of each isoform to mucosal prostaglandin synthesis in various circumstances is not clear. In the normal stomach, only COX-1 is expressed in detectable amounts.…”

Section: Discussionmentioning

confidence: 99%

Aspirin causes rapid up‐regulation of cyclo‐oxygenase‐2 expression in the stomach of rats

Davies

Sharkey

Asfaha

et al. 1997

Aliment Pharmacol Ther

125

View full text Add to dashboard Cite

Background:Cyclo‐oxygenase‐1 (COX‐1) is believed to produce prostaglandins vital to mucosal defence, whereas cyclo‐oxygenase‐2 (COX‐2) is induced at sites of inflammation. Little is known about the regulation of COX‐2 in the stomach, particularly during the period following mucosal injury. In this study, we examined COX‐1 and COX‐2 expression shortly after administration of NSAIDs or ethanol.Methods:Fasted rats were given aspirin, salicylate, indomethacin or ethanol (20% or 40%) orally. Three hours later the stomach was excised, the severity of damage scored and samples taken for RT‐PCR of COX‐1 and COX‐2 mRNA and immunohistochemistry. Nitric oxide synthase mRNA (iNOS and eNOS) and activity were also measured.Results:Aspirin, indomethacin and the higher concentration of ethanol produced widespread mucosal damage, whereas salicylate and 20% ethanol caused only superficial epithelial damage. Aspirin caused a significant increase in COX‐2 mRNA expression and a marked increase in COX‐2 immunoreactivity, particularly in the superficial mucosa. Expression of COX‐1 (mRNA and protein) was unaffected by aspirin, as were NOS mRNA expression and enzyme activity. Pre‐treatment with prostaglandin E2 prevented the induction of COX‐2 by aspirin. Salicylate and indomethacin caused modest increases in COX‐2 immunoreactivity but no change in COX‐2 mRNA. Neither concentration of ethanol affected COX‐2 mRNA or protein expression, suggesting that this was a specific response to the aspirin, rather than to injury.Conclusions:These results demonstrate a rapid up‐regulation of COX‐2 expression in response to aspirin, possibly representing a compensatory response to inhibition of gastric prostaglandin synthesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Aspirin causes rapid up‐regulation of cyclo‐oxygenase‐2 expression in the stomach of rats

Davies

Sharkey

Asfaha

et al. 1997

Aliment Pharmacol Ther

125

View full text Add to dashboard Cite

show abstract

“…This could occur via an EFA-induced increase in PGE, production; exogenous PGE1 has been shown to accelerate gastrointestinal repair by increasing cell proliferation rates (Levi et al, 1990). It may also reflect a direct action of EFAs which are required for membrane synthesis in proliferating cells.…”

Section: Discussionmentioning

confidence: 99%

The modulation of radiation-induced damage to pig skin by essential fatty acids

Hopewell

Robbins²,

Aardweg³

et al. 1993

Br J Cancer

View full text Add to dashboard Cite

The ability of essential fatty acids (EFAs) to modulate radiation-induced normal tissue injury was assessed in pig skin. Female Large White pigs (approximately 25 Kg) received 3 ml/day orally of either an 'active' oil [So-1100, containing 9% gamma-linolenic acid (GLA)] or a 'placebo' oil (So-1129) for just 4 weeks before or for 4 weeks before and for 16 weeks after irradiation; localised irradiation of skin was with single doses of beta-rays from 22.5 mm diameter 90Sr/90Y plaques. The severity of the acute reaction, assessed in terms of erythema or moist desquamation, was significantly less in those pigs that received So-1100 both before and after irradiation, as compared with those receiving that oil only prior to irradiation and the 'placebo' groups. Dose modification factors (DMFs) of between 1.13-1.24 were obtained. A similar reduction in the severity of acute skin injury was seen in pigs receiving So-1100 for only 10 weeks after irradiation. Late skin damage, assessed in terms of late erythema or dermal necrosis, was also reduced with So-1100, with DMFs of 1.14-1.51. No such modification was observed if So-1100 was only administered for 4 weeks prior to irradiation. No adverse side-effects were apparent as a result of EFA administration. So-1100 may represent a safe and valuable method of increasing the therapeutic gain in radiotherapy.

show abstract

“…These results appear to support our hypothesis that indomethacin treatment prevents the contraction of the ulcer base, leading to delayed ulcer healing. Levi et al (20) reported that indo methacin inhibited the proliferation of mucosal cells around the cryoprobe-induced gastric ulcers in the rat. In the present study, we found that indomethacin had no effect on mucosal regeneration.…”

Section: Discussionmentioning

confidence: 99%

Mechanism by Which Indomethacin Delays Gastric Ulcer Healing in the Rat: Inhibited Contraction of the Ulcer Base

Ogihara

Okabe

1993

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

Inhibitory effect of non-steroidal anti-inflammatory drugs on mucosal cell proliferation associated with gastric ulcer healing

Cited by 173 publications

References 13 publications

Aspirin causes rapid up‐regulation of cyclo‐oxygenase‐2 expression in the stomach of rats

Aspirin causes rapid up‐regulation of cyclo‐oxygenase‐2 expression in the stomach of rats

The modulation of radiation-induced damage to pig skin by essential fatty acids

Mechanism by Which Indomethacin Delays Gastric Ulcer Healing in the Rat: Inhibited Contraction of the Ulcer Base

Contact Info

Product

Resources

About