Early Vascular Injury and Increased Vascular Permeability in Gastric Mucosal Injury Caused by Ethanol in the Rat

Szabó, Sándor; Trier, Jerry S.; Brown, A. J.; Schnoor, Julie

doi:10.1016/s0016-5085(85)80176-1

Cited by 453 publications

(249 citation statements)

References 17 publications

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“…Dose of 1 g.kg -1 of crude extract presuppose the presence of the active principle in concentration of 10% for substances like cimetidine (100 mg.kg -1 ), 2% for those similar to omeprazol (20 mg.kg -1 ) and of 0.1% for those like misoprostol (1 mg.kg -1 ), taking into consideration the dosage employed in antiulcer therapeutics (Brito 1996). Szabo et al (1985) demonstrated the onset of vascular injury in the glandular mucosa of the rat stomach within one minute after the intragastric administration of ethanol. The pathogenesis of the vascular lesions is not known but may be partly related to a direct effect of ethanol and its metabolites on endothelial cells.…”

Section: Resultsmentioning

confidence: 97%

Antiulcerogenic activity of Indigofera truxillensis Kunth

et al. 2006

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Cola-Miranda, M; Barbastefano, V.; Hiruma-Lima, C.A.; Calvo, T.R.; Vilegas, W. and Brito, A.R.M.S. Antiulcerogenic activity of Indigofera truxillensis Kunth. Biota Neotrop. Sep/Dec 2006 vol. 6, no. 3 http://www.biotaneotropica.org.br/v6n3/ pt/abstract?article+bn01006032006 ISSN 1676-0611The genus Indigofera (Fabaceae) is used in folk medicine to treat gastrointestinal pain. In this study, we investigated the antiulcerogenic properties of Indigofera truxillensis Kunth. Oral administration of MeOH extract did not produce any signals of acute toxicity. The antiulcerogenic activity was assessed in different models of acute gastric ulcers (100% ethanol, piroxicam 30 mg.kg -1 , hypothermic restraint stress and pylorus ligature) in mice and rats. The animals were treated with the drugs lanzoprazole (30 mg.kg -1 ) or cimetidine (100 mg.kg -1 ) as positive controls depending on the performed model. In another experiment with ethanol-induced ulcers in rats, N-ethylmaleimide (NEM), a sulfhydryl group blocker, was also used. The MeOH extract, at doses of 250, 500 and 1000 mg.kg -1 , inhibited the gastric lesions in all experiments: a) by 62%, 69% and 32%, respectively, in piroxicam-induced lesions, b) by 43%, 71% and 98%, in ethanol-induced lesions, c) by 69%, 64 and 89%, in hypothermic-restraint stress-induced lesions, d) by 73%, 82% and 84%, in pylorus ligature lesions. Significant changes in the total gastric acid levels were also found after intraduodenal administration of the MeOH extract in the ligated pylorus model. Pre treatment with NEM reduced partially the antiulcerogenic activity of the MeOH extract in ethanolinduced gastric lesions. This result indicates an increase in the levels of non-protein sulfhydryl groups by MeOH extract in the gastric mucosa. These results indicate that the MeOH extract has antisecretory and citoprotective effects that may be related to the presence of flavonoids detected by phytochemical analysis. O gênero Indigofera (Fabaceae) é utilizado na medicina tradicional para distúrbios gastrintestinais. Em nosso trabalho foi investigada a propriedade antiulcerogênica da Indigofera truxillensis Kunth. A administração oral do extrato metanólico (MeOH) não produziu efeitos tóxicos. A atividade antiulcerogênica foi avaliada em diferentes modelos agudos de úlcera gástrica (etanol 100%, piroxicam 30 mg.kg -1 , estresse por retenção e frio e ligadura do piloro) em camundongos e ratos. Os animais foram tratados com lansoprazol (30 mg.kg -1 ) ou cimetidina (100 mg.kg -1 ), que foram utilizados como controle positivo dependendo do modelo testado. Em outro experimento com úlcera induzida por etanol em ratos, N-etilmaleimida (NEM), um bloqueador dos compostos sulfidríla, também foi utilizado. O extrato metanólico, nas doses de 250, 500 e 1000 mg.kg -1 , inibiu significativamente as lesões gástricas em todos os experimentos: a) 62%, 69% e 32%, respectivamente, nas lesões gástricas induzidas por piroxicam, b) 43%, 71% e 98%, nas lesões gástricas induzidas por etanol, c) 69%, 64% e 89%, nas lesões ...

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Section: Resultsmentioning

confidence: 97%

Antiulcerogenic activity of Indigofera truxillensis Kunth

et al. 2006

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“…Szabo et al (26,27) showed the increased vascular permeability in the gastric mucosa damaged by ethanol in rats, and they sug gested that vascular injury is an early pathoge netic factor in the development of ethanol induced gastric hemorrhagic erosions. PGs and sulfhydryls might prevent the increased vascular permeability to exert gastric cyto protection.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1987

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Abstract-The present study was undertaken using acetazolamide (AZ) and cyste amine (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 HCI-ethanol (1 ml of 60% ethanol in 150 mM HCI, 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 inhi bited 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 HCI-ethanol-induced mucosal injury, the correlation coefficient being 0.819 (P< 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 HCI-ethanol, probably through a dissolution of mucosal folds due to inhibition of gastric motor activity.

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“…In addition to vascular spasm, ischaemia and contraction of airway smooth muscle, endothelin-1-induced plasma extravasation with local oedema would induce or predispose to tissue damage. For example, it has been postulated that local oedema formation might directly contribute to bronchial hyperresponsiveness by causing airway narrowing and increasing mucosal thickness (Moreno et al, 1986), might increase the susceptibility of gastric mucosa to damage through causing endothelial injury (Szabo et al, 1985) and might contribute to the development of glomerular injury (Simonson & Dunn, 1991).…”

Section: Discussionmentioning

confidence: 99%

Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor

Filep¹,

Sirois

Rousseau

et al. 1991

British J Pharmacology

106

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The objectives of the present experiments were to assess the effects of endothelin‐1 on the macrovascular permeability in selected vascular beds, to study the involvement of platelet‐activating factor (PAF) in vascular responses to endothelin‐1 and to examine the vascular effects of combined administration of endothelin‐1 and PAF in conscious rats. Intravenous bolus injection of endothelin‐1 (0.1–2 nmol kg−1) resulted in a dose‐dependent biphasic change in mean arterial blood pressure (MABP) with initial transient hypotension followed by a prolonged pressor action. These changes were accompanied by a dose‐dependent increase in haematocrit values. Endothelin‐1 (0.1 and 1 nmol kg−1) increased dose‐dependently the vascular permeability of the trachea, upper and lower bronchi, stomach, duodenum, spleen and kidney (up to 240%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, liver and pancreas was not affected significantly by endothelin‐1 treatment. Pretreatment of animals with the specific PAF receptor antagonist, WEB 2086 (1 mg kg−1, i.v.) or BN 52021 (10 mg kg−1, i.v.) reduced the endothelin‐1 (1 nmol kg−1)‐induced rise in haematocrit by about 50 and 30%, respectively. Both antagonists were highly effective at inhibiting protein extravasation in the stomach, duodenum and kidney. On the other hand, BN 52021, but not WEB 2086, significantly attenuated the effect of endothelin‐1 on permeability in the lower bronchi and spleen. Neither WEB 2086 nor BN 52021 modified the changes in MABP evoked by endothelin‐1. When low doses of endothelin‐1 (0.1 nmol kg−1) and PAF (0.19 nmol kg−1) were administered simultaneously, enhanced protein extravasation was detected in the upper and lower bronchi, whereas neither endothelin‐1 nor PAF by themselves affected vascular permeability in these tissues. These changes occurred in the absence of significant changes in MABP. Combined administration of higher doses of endothelin‐1 (1 nmol kg−1) and PAF (1.9 nmol kg−1) resulted in marked increases (up to 530%) in protein extravasation in the airways, pancreas, stomach and duodenum. The effect of endothelin‐1 on permeability was not affected by PAF in the spleen, whereas it was completely inhibited by PAF in the kidney. Combined injection of endothelin‐1 and PAF resulted in a slight, but significant increase in MABP. The present findings show that endothelin‐1 is capable of increasing vascular permeability in selected vascular beds including the airways, gastrointestinal tract and kidney, and suggest that PAF may mediate, in part, its action on permeability, but not its hypotensive action. The present data also suggest that endothelin‐1 and PAF can act in concert to increase vascular permeability in rat airways and gastrointestinal tract.

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Early Vascular Injury and Increased Vascular Permeability in Gastric Mucosal Injury Caused by Ethanol in the Rat

Cited by 453 publications

References 17 publications

Antiulcerogenic activity of Indigofera truxillensis Kunth

Antiulcerogenic activity of Indigofera truxillensis Kunth

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

Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor

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