Adaptation of the gastric mucosa to repeated administration of aspirin in the rat

John, David; Yeomans, Neville D; McDermott, F. T.; Boer, W.G.R.M. de

doi:10.1007/bf01073339

Cited by 82 publications

(12 citation statements)

References 13 publications

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“…Previous clinical and experimental studies have shown that adaptation to the gastric lesion-inducing effects of aspirin can occur during a regimen of repeated administration [12][13][14]. In our study, we did not observe any decrease in fecal blood loss during the 3 days of aspirin administration.…”

Section: Discussionsupporting

confidence: 36%

Rioprostil Prevents Aspirin-Induced Fecal Blood Loss in Dogs

Katz¹,

Fernandez²,

Schwartz³

et al. 1989

Digestion

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Rioprostil, a primary alcohol prostaglandin E₁ analog, prevents gastric lesion formation induced by a variety of irritants, including aspirin, in rats and dogs. In the present study, rioprostil reduced both gastric lesion formation and fecal blood loss in dogs caused by daily aspirin administration (1,950 mg/day) for 3 consecutive days. A gastric antisecretory dose of 100 μg/kg p.o. t.i.d. of rioprostil reduced fecal blood loss by 96% to a level (0.76 ± 0.10 mg Hb/g stool) similar to basal blood loss in non-aspirin-treated vehicle dogs (0.61 ± 0.08 mg Hb/g stool) as determined by HemoQuant® assay. A nonantisecretory dose of rioprostil (1 μg/kg p.o. t.i.d.) reduced fecal blood loss by 70% compared to vehicle-treated dogs. Gastric lesion severity scores in dogs treated with 100 or 1 μg/kg p.o. t.i.d. of rioprostil were 61 and 52% lower, respectively, than the mean severity score in the vehicle-treated group. There was a highly significant (p < 0.001) correlation between gastric lesion score and fecal blood loss independent of the treatment each dog received. The efficacy of a nonantisecretory dose suggests that the gastric lesion effect of rioprostil may be independent of gastric antisecretory effects. The correlation of fecal blood loss with gastric lesion score suggests the possibility that either measurement may be used as an indication of gastric lesion occurrence or severity.

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Section: Discussionsupporting

confidence: 36%

Rioprostil Prevents Aspirin-Induced Fecal Blood Loss in Dogs

Katz¹,

Fernandez²,

Schwartz³

et al. 1989

Digestion

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“…Similarly, measurable increases in TGF-␣ and epidermal growth factor also occur in adapted stomachs only after multiple doses of aspirin and not after a single injurious dose (Doljanin et al, 1996;Konturek et al, 1994aKonturek et al, , 1998aRomano et al, 1996). It is possible that the increments in mucosal RegI (and indeed TGF-␣ and epidermal growth factor) that occur as a result of each adapting dose finally culminate as an "effective" increase only after several episodes of daily injury-this would help to explain the lag time of several days required for the onset of adaptation St John et al, 1973;Wallace et al, 1995).…”

Section: Alderman Et Almentioning

confidence: 99%

“…This phenomenon was later termed "adaptation" (St John et al, 1973) and has since been observed after the repeated administration of a number of different NSAIDs in both humans (Graham et al, 1983;Lipscomb et al, 1995;Shorrock et al, 1990) and experimental animals (Skeljo et al, 1992. Despite being observed and quantified for many decades, the precise mechanisms and mediators of adaptation remain unclear, but some contributory factors are beginning to be uncovered.…”

mentioning

confidence: 99%

Insights into the Mechanisms of Gastric Adaptation to Aspirin-Induced Injury: A Role for Regenerating Protein but Not Trefoil Peptides

Alderman

Ulaganathan

Judd

et al. 2003

Laboratory Investigation

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SUMMARY:The phenomenon of reduced gastric mucosal injury despite repeated doses of a damaging agent is termed adaptation. Adaptation to nonsteroidal anti-inflammatory drug-induced injury has been clearly demonstrated in both humans and experimental animals; however, the precise mechanisms remain unclear. We hypothesized that mediators of adaptation might be the regenerating protein (RegI) and the trefoil peptides TFF1 and TFF2, because these proteins play pivotal roles in gastric mucosal protection and repair. The gene expression and the protein levels of these proteins were measured and compared in normal, aspirin-injured, and aspirin-adapted rat stomachs. TFF gene and protein expression levels were similar in all three groups, whereas RegI gene expression and protein levels in adapted stomach were increased. A time course analysis of RegI expression during the onset and offset of adaptation showed that mucosal RegI increased during the development of adaptation, was maintained during subsequent aspirin dosing, and returned to baseline levels once dosing had ceased and adaptation was lost-indicative of a causal role in the adaptation process. Colocalization of increased RegI with gastric epithelial areas showing increased proliferation also suggests that RegI may be an important mediator of the resolution of mucosal injury that is characteristic of gastric adaptation to aspirin. (Lab Invest 2003, 83:1415-1425.

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“…Instead, the gastnc mucosa may develop resistance or 'tolerance' to the ulcerogenic agents. This occurs in both humans and antmals and h,ls been demonstrated for ASA as well as for ethanol (49)(50)(51)(52).…”

Section: Trophic Effects Of Prost Aglandinsmentioning

confidence: 99%

Prostaglandins and Mucosal Defensive Mechanisms

Morris¹,

Williamson²,

Hynna³

1990

Canadian Journal of Gastroenterology

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The first line of mucosa! defence includes the juxtamucosal unstirred layer/pl I gradient and the apical surface~ of the luminal epithelial cells.Many damag ing age nts, including n onsteroidnl anti-inflammatory drugs (NSAIDs), can overwhelm Lhese defences and destroy ex tensive regions of the luminal cpiLhe lium. This damage is readily L olerated in the normal mucosa. Furthermore, a combination of inc reased mucosa! bloodflow, epi thelial migration, mucus release, and efflu x of bicarbonate-rich fluid usua lly allows rapid recovery of mucosa I integrity. In th e presence of vasc ular damage and congestion, however, luminal acid can kill mucosa! cells and destroy the substrate necessary for repair (by epithelial migration ). Damage of this type results in the production of hemorrhag ic erosion s, which may then develop into chronic ulceroinflammatory disease if healing is prevented by exec&, lu minal ac id or by impaired mucosa! immune response. Endogenous and exogenous prostaglandins could affect all aspects of the mucosa! defensive response~, fro m the juxcam ucosal unstirred layer/pH gradient ( via effects on secretion of bicarbonate, acid and mucus, as well as stimulation of fluid efflux) to the function of the mucosa! immune system. Protection against the acute damage produced by topically administered NSAIDs or concentrated etha nol can result from e ither administration of prostaglandins or topical applicaLion of'mild irritants'. This is referred to as 'adaptive cytopr~tection'. Parenterally adm in istereJ NSAIDs can also produce mucosa! erosions. Proteclion aga inst this type of damage may depend on the effects of proscaglandins on neura l and contractile elements in the mucosa. Studies on animal models also suggest that by preventing ac ute hemorrhagic erosions, prostaglandins may prevent the development of chronic ulcer in susceptible individuals. Can J Gastroenterol 1990;4(3 ):95 -107

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Adaptation of the gastric mucosa to repeated administration of aspirin in the rat

Cited by 82 publications

References 13 publications

Rioprostil Prevents Aspirin-Induced Fecal Blood Loss in Dogs

Rioprostil Prevents Aspirin-Induced Fecal Blood Loss in Dogs

Insights into the Mechanisms of Gastric Adaptation to Aspirin-Induced Injury: A Role for Regenerating Protein but Not Trefoil Peptides

Prostaglandins and Mucosal Defensive Mechanisms

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