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Titolo:
New model of cytoprotection adaptive cytoprotection in rats: endogenous small irritants, antiulcer agents and indomethacin
Autore:
Sikiric, P; Seiwerth, S; Deskovic, S; Grabarevic, Z; Marovic, A; Rucman, R; Petek, M; Konjevoda, P; Jadrijevic, S; Sosa, T; Perovic, D; Aralica, G; Turkovic, B;
Indirizzi:
Univ Zagreb, Med & Vet Fac, Ctr Digest Dis, Zagreb 41000, Croatia Univ Zagreb Zagreb Croatia 41000 , Ctr Digest Dis, Zagreb 41000, Croatia
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 1, volume: 364, anno: 1999,
pagine: 23 - 31
SICI:
0014-2999(19990101)364:1<23:NMOCAC>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
PENTADECAPEPTIDE BPC-157; RESTRAINT STRESS; PEPTIDE; CYSTEAMINE; LESIONS; ETHANOL; INJURY; ORGANOPROTECTION; PROSTAGLANDINS; PROTECTION;
Keywords:
irritant, endogenous, small; cytoprotection; cytoprotection, adaptive; surgery; anastomosis; pentadecapeptide BPC 157; omeprazole; antiulcer agents; (rat);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Sikiric, P Univroatiab, Fac Med, Dept Pharmacol, Salata 11,POB 916, Zagreb10000 HR, C Univ Zagreb Salata 11,POB 916 Zagreb Croatia 10000 HR 00 HR, C
Citazione:
P. Sikiric et al., "New model of cytoprotection adaptive cytoprotection in rats: endogenous small irritants, antiulcer agents and indomethacin", EUR J PHARM, 364(1), 1999, pp. 23-31

Abstract

Adaptive cytoprotection in the stomach was originally defined by applying the exogenous irritants only. The contribution of endogenous irritants as inductors of initial lesions was not specially evaluated. No attempt was made to either focus antiulcer agent activity on adaptive cytoprotection, or split their 'cytoprotection' into complex adaptive cytoprotective activity and simple cytoprotective effects. Agents had so far not been applied simultaneously with the second challenge with ethanol (or irritant), when differences between cytoprotection and adaptive cytoprotection appear. Gastrojejunal anastomosis for 24 h in rats was introduced as new model for analyzing cytoprotection/adaptive cytoprotection. The contribution of the up-normal level of endogenous irritants and the endogenous small irritant-induced minorlesions during the adaptive cytoprotection were studied. The effect of late challenge with 96% ethanol in the presence of an up-normal level of endogenous irritants and endogenous small irritant-induced minor lesions was compared with results of classic studies of ethanol-induced gastric lesions innormal rats (1 ml/rat i.g.). Antiulcer agents or a prostaglandins-synthesis inhibitor, indomethacin, given once only in classic studies, were given at several points during injury induction: (i) surgery, (ii) mild ethanol, (iii) strong ethanol, (iv) strong ethanol applied after a suitable period following either mild ethanol or surgery). Their effects were compared in rats treated as follows: exogenous irritant studies (96% or 20% ethanol), exogenous/exogenous irritant studies (20% ethanol 1 h before 96% ethanol), endogenous irritant studies (gastrojejunal anastomosis for 24 h), and endogenous/exogenous irritant studies (gastrojejunal anastomosis for 24 h before 96%ethanol). Characteristic of the various irritants differed: the (preceding) small irritants (exogenous (i.e., mild ethanol in healthy intact rats) (exogenous irritant studies) vs, endogenous (e.g., (increased) gastric acid secretion, duodenal reflux in gastric content in rats with termino-lateral gastrojejunal anastomosis) (endogenous irritant studies)). These factors caused modifications of agents' activities not, as initially thought, giving simple 'cytoprotection', but being only cytoprotective, or adaptive cytoprotective, or both cytoprotective and adaptive cytoprotective. Atropine (10 mg/kg i.p.) and ranitidine (10 mg) had only cytoprotective activity (exogenous irritant-studies), whereas pentadecapeptide BPC157 (10 mu g or 10 ng), and omeprazole (10 mg) had mainly adaptive cytoprotective activity (endogenous/exogenous irritant studies) or both cytoprotective and adaptive cytoprotective activities (exogenous/exogenous irritant studies). Augmentation of the lesions by indomethacin (5 mg/kg s.c.), showed that only events precedingthe late challenge with ethanol may be prostaglandin-dependent in both models. The second, adaptive cytoprotective part, seen after late ethanol challenge, may be either prostaglandin-dependent (exogenous/exogenous irritant studies) or non-dependent (endogenous/exogenous irritant studies). Both spontaneous lesion reduction, as an essential mechanism of adaptive cytoprotection, and the further lesion reduction by agents, such as pentadecapeptide BPC 157 and omeprazole, suggests that these agents function as an essentiallink between the various reactions in cytoprotection/adaptive cytoprotection. (C) 1999 Elsevier Science B.V. All rights reserved.

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Documento generato il 19/09/20 alle ore 14:48:24