Influence of prostaglandin on repair of rat stomach damaged by absolute ethanol

Kl, Schmidt; Rl, Bellard; Gs, Smith; Jm, Henagan; Ta, Miller

doi:10.1016/0022-4804(86)90050-8

Cited by 12 publications

(10 citation statements)

References 9 publications

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“…With time, acid secretion slowly reappeared; however, at 2 days after ethanol, the acid concentration had returned to only 50% of the control value (p<001 v control) and acid output to only 73% of the control value (p<005 v control). The dmPGE2, by itself, had no effect on gastric acid secretion at this low dose of 10 .tg/kg (group II). Animals given dmPGE2 30 minutes before absolute + ethanol always secreted significantly more acid than those given only absolute ethanol, regardless of when the gastric juice was collected (from 4 hours to 2 days after administration of absolute ol ethanol) (Figs 1 and 2, group IV).…”

Section: Studies In Conscious Animalsmentioning

confidence: 86%

Morphological and functional gastric cytoprotection by prostaglandin in rats receiving absolute ethanol orally.

Robert

Leung

Guth

1992

Gut

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Pretreatment with prostaglandins at non-antisecretory doses protects the gastric mucosa, including the parietal cells, from deep necrosis produced by intragastric administration of necrotising agents such as absolute ethanol. Whether the parietal cells also retained their ability to secrete acid when rats were pretreated with a prostaglandin, in spite of exposure to ethanol, was investigated. Gastric acid secretion was abolished 4 hours after ethanol, and secretion returned to control values only after 5-6 days. Pretreatment The aims of the present studies were to determine whether (a) the secretory impairment is due to the extensive damage to the parietal cells produced by ethanol, and (b) dmPGE2 maintains the acid secretory function of the parietal cells by preserving their morphological integrity. The time course of secretory and morphological (histological) changes induced by ethanol in control and prostaglandin-pretreated animals was also determined to establish a correlation between the structure and function of parietal cells. To this end, gastric acid secretion and histological injury were measured at various times after oral administration of absolute ethanol in rats, with and without pretreatment with dmPGE2 given at cytoprotective doses (that is non-antisecretory doses). The changes in secretion were correlated with the extent of gastric damage assessed by quantitative histology. These experiments were conducted in rats whose stomach was stimulated to secrete by either carbachol, pentagastrin, histamine, or vagal electrical stimulation. MethodsMale and female Sprague-Dawley rats of 220-320 g were fasted for 24 hours. During the last 18 hours, they were placed in individual cages to prevent coprophagy, and drinking water was removed. In the gastric secretory studies, gastric juice was collected from conscious and anaesthetised rats. In conscious animals, gastric secretion was collected after pylorus ligation and carbachol stimulation, a procedure that yields large amounts of acid. Anaesthetised rats with gastric fistulas were also used because the basal values being very low, individual secretagogues acting by different mechanisms (histamine, pentagastrin, vagal, electrical stimulation) can be studied separately. These studies were approved by the Animal Welfare Committee.

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Section: Studies In Conscious Animalsmentioning

confidence: 86%

Morphological and functional gastric cytoprotection by prostaglandin in rats receiving absolute ethanol orally.

Robert

Leung

Guth

1992

Gut

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“…These authors reported a 20% reduction in the depth oftissue injury if PGE, pretreatment had been rendered. Subsequently, several reports have noted histological differences between the ethanol-treated gastric mucosa from animals with and without PGE2 pretreatment (4,12,17,18,20,22).…”

Section: Discussionmentioning

confidence: 98%

“…Other criteria indicative of tissue injury included epithelial cell exfoliation, dilatation ofgland luminae, hyperemia, or hemorrhage. An additional category, denoted as repair, was developed by Schmidt et a1 (17) and was used in the repair study (Table I). Repair was indicated by the presence at the gastric luminal surface or on the gastric pit walls of flattened surface mucous cells, criteria indicating cell migration.…”

Section: Anin~alsmentioning

confidence: 99%

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Morphological Characteristics of Prostaglandin Cytoprotection

Schmidt¹,

Miller

1988

Toxicol Pathol

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The term "cytoprotection" originally described the ability of prostaglandins, independent of their known antisecretory activity, to prevent macroscopic evidence of gastric injury induced in different animal models under various experimental conditions. Several recent reports have challenged this concept because the apparent macroscopic protection could not be confirmed microscopically. To determine whether prostaglandins do indeed possess cytoprotective properties, and if such effects are dependent on the dose and the route of prostaglandin administration, studies were performed using 16,16 dimethyl prostaglandin E2 (PGE2) and the known gastric damaging agent, ethanol. Fasted rats received either oral or subcutaneous PGE2 in doses of 10 or 20 micrograms/kg or equal volumes of saline. Thirty minutes later, animals were given a 1-ml oral bolus of 50% or 100% ethanol or an equal volume of saline. At 5 minutes to 24 hours following ethanol, animals were sacrificed, and tissues from the glandular portion of the stomach were removed for histologic quantification of injury. At 5 minutes following ethanol, PGE2 reduced the depth of injury, but had no protective effects against surface cell damage when compared with control animals. By 24 hours after ethanol, most of the PGE2-treated mucosa was repaired. Oral administration of 10 micrograms/kg PGE2 was more cytoprotective at 5 minutes after ethanol than when administered by subcutaneous injection. This relationship was not true for the 20 micrograms/kg dose. We conclude that cytoprotection can be confirmed histologically, but is limited primarily to the deep mucosa. The ability of PGE2 to enhance healing is probably related to the prevention of deep mucosal injury, which thereby allows epithelial reconstitution to occur. Lastly, the effectiveness of PGE2 as a cytoprotective agent is dose- and route-dependent.

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“…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.…”

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

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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.

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Influence of prostaglandin on repair of rat stomach damaged by absolute ethanol

Cited by 12 publications

References 9 publications

Morphological and functional gastric cytoprotection by prostaglandin in rats receiving absolute ethanol orally.

Morphological and functional gastric cytoprotection by prostaglandin in rats receiving absolute ethanol orally.

Morphological Characteristics of Prostaglandin Cytoprotection

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

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