Wyniki wyszukiwania - Biblioteka Nauki

1

Kwas acetylosalicylowy: wczoraj, dziś, jutro

100%

Dołżenko M. N.

Pediatria i Medycyna Rodzinna

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2014

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tom 10

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nr 2

137-151

EN

Clinical utility of aspirin (acetylsalicylic acid, ASA) is one of the more important issues in the primary and secondary prevention of cardiovascular disease. The present paper provides analysis of aspirin history, mechanisms of its antiplatelet activity, and expediency of the use of low- and high-dose aspirin in the groups including patients after myocardial revascularization, and requiring secondary prevention of stroke. Also gender-specific aspirin properties were mentioned, highlighting the especially important role of aspirin in women at the age of >65 years, and its utility in all women, irrespectively of age, and those who are at high risk of cardiovascular disease, including atherosclerosis-related cardiovascular disease. Moreover, the mechanisms of aspirin resistance, characterized by inability of aspirin to prevent thromboembolic complications or inadequate platelet inhibition showed in laboratory results, were mentioned. Prevalence of resistance in aspirin-treated patients is estimated to be between 1 and 68%. Stress was also put on the aspirin safety, associated with prophylaxis of peptic ulcer disease, which can be achieved i.e. by the use of the enteric-coated aspirin. This form of aspirin is associated with lower risk of gastrointestinal mucosae damage and bleeding from the gastrointestinal tract. At the end of the article, the importance of the adherence to therapeutic guidelines of aspirin use, including assessment of variation in aspirin bioavailability associated with improper dosing and altered absorption in the gastrointestinal tract, was stressed.

PL

Zastosowanie kwasu acetylosalicylowego we wspołczesnej praktyce klinicznej jest jednym z podstawowych założeń pierwotnej i wtornej prewencji chorob układu sercowo-naczyniowego. W artykule przeanalizowano historię problemu, mechanizm efektywności przeciwpłytkowej kwasu acetylosalicylowego, celowość zastosowania jego wysokich i niskich dawek, a także wykorzystanie u pacjentow z nadciśnieniem tętniczym, po zabiegach rewaskularyzacji mięśnia sercowego oraz w profilaktyce udaru mozgu. Odniesiono się rownież do właściwości kwasu acetylosalicylowego zależnych od płci, podkreślając szczegolnie istotny wpływ u kobiet w wieku powyżej 65 lat oraz podając zalecenie stosowania u kobiet w każdym wieku, w tym u młodych, z podwyższonym ryzykiem rozwoju chorob układu sercowo-naczyniowego, m.in. Związanych z procesem miażdżycowym. Przeanalizowano także kwestię oporności na kwas acetylosalicylowy, ktora charakteryzuje się zarowno jego niezdolnością do zapobiegania rozwojowi powikłań zakrzepowych, jak i do adekwatnego tłumienia funkcji płytek krwi ocenianego w badaniach laboratoryjnych. Częstość ujawniania oporności na kwas acetylosalicylowy u chorych, ktorzy go stosują, waha się w zakresie 1–68%. Zwrocono uwagę na profilaktykę powikłań stosowania kwasu acetylosalicylowego związanych z rozwojem choroby wrzodowej – możliwe jest np. przyjmowanie postaci dojelitowej leku, ktora nieco zmniejsza ryzyko uszkodzeń śluzowki żołądka i krwotokow żołądkowo-jelitowych. Duże znaczenie ma przestrzeganie zaleceń terapeutycznych dotyczących kwasu acetylosalicylowego, tzn. należy uwzględniać możliwość obniżenia jego biodostępności w wyniku nieprzestrzegania zaleceń terapeutycznych, nieodpowiedniego sposobu dozowania albo zaburzeń jego wchłaniania w przewodzie pokarmowym.

2

Gastric mucosal protection: from the periphery to the central nervous system

100%

Gyires K. , Toth V. E. , Zadori Z. S.

Journal of Physiology and Pharmacology

|

2015

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tom 66

|

nr 3

3

Angiotensin metabolism in rat stomach wall: prevalence of angiotensin-(1-7) formation

84%

Olszanecki R. , Madej J. , Suski M. , Gebska A. , Bujak-Gizycka B. , Korbut R.

Journal of Physiology and Pharmacology

|

2009

|

tom 60

|

nr 1

191-196

EN

Our view of renin-angiotensin system (RAS) has changed over the past two decades: new metabolites and pathways have been described; also the importance of local renin-angiotensin systems became more clearly understood. However, there is relatively scarce information about formation and action of angiotensin peptides in gastrointestinal tract, especially in the stomach. Here, using LC-ESI-MS method we assessed the metabolism of Ang I in organ bath of rat stomach wall. Additionally we compared the expression of mRNA of angiotensin converting enzymes (ACE, ACE2) and neprilysin (NEP) in the stomach, aorta and renal artery in rats. Despite, similar levels of expression of ACE and ACE2 mRNA in stomach wall, aorta and renal artery, the absolute amounts of main Ang I metabolites produced by stomach wall (in ng/mg of dry tissue) were much lower than that produced by aorta and renal artery. Also, the pattern of angiotensin I metabolites was different: opposite to aorta and renal artery, incubation of Ang I with stomach wall fragments resulted in predominant formation of Ang-(1-7) and relatively lower production of Ang II. In stomach wall both, perindoprilat and tiorphan decreased production of Ang II, but did not influence generation of Ang-(1-7). In conclusion, we identified Ang-(1-7) as the main product of Ang I conversion in rat stomach wall. The biological role of prevalence of Ang-(1-7) formation in stomach require further investigation.

4

Role of polyamines in gastroprotection induced by epidermal growth factor

84%

Brzozowski T. , Drozdowicz D. , Majka J. , Polonczyk-Pytko J. , Konturek S. J.

Journal of Physiology and Pharmacology

|

1991

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tom 42

|

nr 2

EN

Polyamines have been shown to stimulate cellular growth and differentiation, though their role in the prevention of acute gastric lesion induced by various noxious agents has been little studied. Epidermal growth factor (EGF) exhibits gastroprotective and ulcer healing properties due to its potent mitogenic and growth promoting action. This study was designed to compare the gastroprotective effects of spermine and EGF against gastric damage induced by absolute ethanol, acidified aspirin and stress and to determine the role of endogenous polyamines in EGF-induced gast- troprotection. Spermine and EGF significantly reduced the lesions induced by all three ulcerogens. Oral administration of spermine or subcutaneous infusion of EGF in 24 h fasted rats with chronic gastric fistula resulted in similar inhibition of gastric acid and pepsin secretion. Pretreatment with difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), a hey enzyme in the biosynthesis of polyamines, did not affect ethanol lesions, but reversed the protective effect EGF but not spermine, against ethanol. This finding indicates that polyamines mediate, at least in part, EGF-induced gastroprotection. In tests with oral administration of aminoguanidine that is known to suppress the activity of diamino-oxidase (DAO) and to inhibit the degradation of polyamines, EGF showed a markedly enhanced gastroprotective activity against ethanol damage. Since indomethacin failed to affect the gastroprotective effects of spermine and EOF and neither of these agents influenced the mucosal generation of PGE₂ in intact or injured gastric mucosa, we conclude that prostaglandins are not the major factors in spermine- and EGF-induced gastroprotection. This study demonstrates that polyamines are highly effective against gastric lesions induced by various ulcerogens and that they act as primary mediators of EGF-induced gastroprotection.

5

Brain-gut axis in gastroprotection by leptin and cholecystokinin against ischemia-reperfusion induced gastric lesions

84%

Brzozowski T. , Konturek P. C. , Pajdo R. , Kwiecien S. , Ptak A. , Sliwowski Z. , Drozdowicz D. , Pawlik M. , Konturek S. J. , Hahn E. G.

|

2001

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tom 52

|

nr 4,1

EN

Leptin, a product of ob gene controlling food intake, has recently been detected in the stomach and shown to be released by CCK and implicated in gastroprotection against various noxious agents but it is unknown whether centrally applied leptin influences ischemia-reperfusion (I/R)-induced gastric erosions that progress into deeper gastric ulcerations. In this study we compared the effects of leptin and CCK-8 applied intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) on gastric mucosal lesions induced by I/R and topical application of 75% ethanol. Several major series of Wistar rats were used to examine the effects of leptin and CCK applied centrally on gastroprotection against I/R and ethanol in rats with A) vagotomy by cutting of vagal nerves, B) suppression of NO-synthase with L-NNA (20 mg/kg i.p.), C) inactivation of sensory nerves by capsaicin (125 mg/kg s.c.) and D) inhibition of CGRP receptors with CGRP8-37 (100 µg/kg i.p.) applied with or without the i.c.v. pretreatment with leptin or CCK-8. Rats were anesthetized 1 h after ethanol administration or at 3 h and 3 days upon the end of ischemia to measure the gastric blood flow (GBF) and then to determine the area of gastric lesions by planimetry. Blood was withdrawn for the measurement of plasma leptin and gastrin levels by radioimmunoassay (RIA). Leptin (0.1—20 µg/kg i.p.) dose-dependently attenuated gastric lesions induced by 75% ethanol and I/R; the dose reducing these lesions by 50% (ED50) was 8 µg/kg and 6 µg/kg, respectively and this protective effect was similar to that obtained with CCK-8 applied in a standard dose of 10 µg/kg i.p. This protective effect of leptin was accompanied by a significant increase in GBF and plasma gastrin levels whereas CCK-8 increased plasma leptin levels but failed to affect plasma gastrin levels. Leptin and CCK-8 applied i.c.v. in a dose of 625 ng/rat reduced significantly the area of I/R induced gastric lesions and raised the GBF and plasma leptin levels with the extent similar to those achieved with peripheral administration of leptin or CCK-8 (10 µg/kg i.p.). The protective and hyperemic effects of centrally administered leptin or CCK-8 (625 ng/rat i.c.v.) were completely abolished by vagotomy and significantly attenuated by sensory denervation with capsaicin or by CGRP antagonist, CGRP8-37. The pretreatment with L-NNA to inhibit NO-synthase activity attenuated significantly the protective and hyperemic effects of CCK but not those of leptin while capsaicin denervation counteracted leptin-- induced protection and rise in the GBF but attenuated significantly those of CCK. We conclude that: 1) central leptin exerts a potent gastroprotective activity against I/R-induced gastric erosions that progress into deeper gastric lesions and this protection depends upon vagal activity and sensory nerves and involves hyperemia probably mediated by NO and 2) leptin mimics the gastroprotective effect of CCK and may be implicated in the protective and hyperemic actions of this peptide against mucosal damage evoked by I/R.

6

Studies on gastroprotection induced by capsaicin and papaverine

84%

Brzozowski T. , Drozdowicz D. , Majka J. , Konturek S. J.

Journal of Physiology and Pharmacology

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1992

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tom 43

|

nr 4

EN

Capsaicin and papaverine are potent vasorelaxants with strong gastroprotective activity against damage induced by absolute ethanol. This protection was originally attributed to the increase in gastric mucosal blood flow (GBF) but the possibility that NO mediates the protective and hyperemic effects of capsaicin and papaverine has been little studied. Using N-nitro-L-arginine (L-NNA), a selective blocker of NO synthase, and L-arginine as a substrate for NO, we investigated the role of NO in protective action of capsaicin and papaverine against ethanol-induced gastric damage and in GBF. Pretreatment with capsaicin (0.1-0.5mg/kg i. g.) or papaverine (0.1-2mg/kg i.g.) reduced dose-dependently the area of ethanol- induced lesions, the LD50 being 0.3 and 1 mg/kg, respectively. This protection was accompanied by a gradual increase in the GBF. Intravenous (i. v.) injection of L-NNA (1.2-5 mg/kg), which by itself caused only a small increase in ethanol lesions, reversed dose-dependently the protective and hyperemic effects of capsaicin and papaverine against ethanol-induced damage and attenuated the increase in GBF induced by each of these agents alone. This deleterious effect of L-NNA on the gastric mucosa and the GBF was fully antagonized by L-arginine (200 mg/kg i. v.) but not by D-arginine. L-arginine partly restored the decrease in GBF induced by L-NNA. Pretreatment with indomethacin (5 mg/kg i.p.), which suppressed the generation of PG by 85%, slightly enhaced the mucosal lesions induced by ethanol but failed to affect the fall in GBF induced by this irritant. Gastroprotective and hyperemic effects of capsaicin and papaverine were partly reversed by indomethacin suggesting that endogenous PG are also implicated in these effects. Addition of L-NNA to indomethacin completely eliminated both the protective and hyperemic effects of capsaicin and papaverine. We conclude that both NO and PG contribute to the gastroprotective and hyperemic effects of capsaicin and papaverine on the gastric mucosa.

7

Brain-gut axis in gastroprotection by leptin and cholecystokinin [CCK]

84%

Brzozowski T. , Ptak A. , Kwiecien S. , Sliwowski Z. , Pajdo R. , Drozdowicz D. , Konturek P. C. , Konturek S. J. , Hahn E. G.

Journal of Physiology and Pharmacology. Supplement

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2001

|

tom 52

|

nr 2

8

Importance of brain-gut axis in the gastroprotection induced by gastric and remote preconditioning

84%

Brzozowski T. , Konturek P. C. , Pajdo R. , Kwiecien S. , Sliwowski Z. , Drozdowicz D. , Ptak-Belowska A. , Pawlik M. , Konturek S. J. , Pawlik W. W. , Hahn E. G.

Journal of Physiology and Pharmacology

|

2004

|

tom 55

|

nr 1,2

EN

Limitation of the damage to the organs such as heart, liver, intestine, stomach and brain by an earlier brief complete occlusion of their arteries is defined as ischemic preconditioning (IP). No study so for has been undertaken to check whether brain-gut axis is involved in the gastroprotection exhibited by gastric IP or in that induced by repeated brief episodes of ischemia of remote organs such as heart and liver. This study was designed to determine the possible involvement of vagal and sensory afferent nerves, in the mechanism of gastric and remote organ IP on the gastric mucosa in rats exposed to prolonged ischemia-reperfusion with or without functional ablation of sensory nerves by capsaicin or in those with removed vagal innervation by vagotomy. This gastric IP was induced by short ischemia episodes (occlusion of celiac artery 1-5 times for 5 min) applied 30 min before subsequent ischemia followed by 3 h of reperfusion (I/R) and compared with remote IP induced by occlusion of left descending coronary artery or hepatic artery plus portal vein. The area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured by H2-gas clearance method and mucosal biopsy samples were taken for the assessment of calcitonin gene-related peptide (CGRP) by RIA. Exposure of gastric mucosa to standard 3 h of I/R produced numerous gastric lesions and significant fall in the GBF and mucosal CGRP content. Two 5 min short ischemic episodes by occlusion of coronary or hepatic arteries, significantly reduced gastric damage induced by I/R with the extent similar to that exhibited by two short (5 min) episodes of gastric ischemia. These protective effects of gastric and remote IPs were accompanied by a restoration of the fall in the CGRP content caused by I/R alone. Protection and hyperemia induced by gastric IP were significantly attenuated in capsaicin-denervated or vagotomized animals and completely removed in those exposed to the combination of vagotomy and capsaicin-denervation. The IP-induced protection and hyperemia were restored by the administration of exogenous CGRP to gastric IP in capsaicin-treated animals. Gastroprotective and hyperemic actions of remote IP were markedly diminished in capsaicin-denervated rats and in those subjected to vagotomy. We conclude that brief ischemia in remote organs such as heart and liver protects gastric mucosa against gastric injury induced by I/R as effectively as gastric IP via mechanism involving both vagal and sensory nerves releasing vasodilatatory mediators such as CGRP.

9

The influence of calcium antagonists [verapamil, nifedipine, and MgCl2] on rat gastric damage induced by ethanol in vivo and in vitro

84%

Ostrowski J. , Pesta J. , Linnik D. , Butruk E.

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nr 3

10

Importance of luminal and mucosal zinc in the mechanism of experimental gastric ulcer healing

67%

Opoka W. , Adamek D. , Plonka M. , Reczynski W. , Bas B. , Drozdowicz D. , Jagielski P. , Sliwowski Z. , Adamski P. , Brzozowski T.

Journal of Physiology and Pharmacology

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2010

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tom 61

|

nr 5

11

Role of prostaglandins in gastroprotection and gastric adaptation

67%

Brzozowski T. , Konturek P. C. , Konturek S. J. , Brzozowska I. , Pawlik T.

Journal of Physiology and Pharmacology. Supplement

|

2005

|

tom 56

|

nr 5

33-55

EN

Since Robert discovery that pretreatment with prostaglandin (PG) applied in non-antisecretory dose can prevent the injury of gastric mucosa induced by necrotizing agents, much attention was paid to the role of these cyclooxygenaxe (COX) products in the mechanism of gastric mucosal integrity and ulcer healing. The ability of exogenous PG to attenuate or even completely prevent mucosal damage caused by corrosive substances such as absolute ethanol, hiperosmolar solutions or concentrated bile has been termed "cytoprotection". Increased generation of endogenous PG in the gastric mucosa exposed to the topical contact with "mild irritant" such as 20% ethanol, 1 mM NaCl or 5 mM taurocholate also prevented gastric injury caused by strong irritants via phenomenon of adaptive cytoprotection. Other mediators such as growth factors, nitric oxide (NO) or calcitonin gene related peptide (CGRP) as well as some gut hormones including gastrin and cholecystokinin (CCK), leptin, ghrelin and gastrin-releasing peptide (GRP) have been also found to protect gastric mucosa against the damage induced by corrosive substances. This protective action of gut hormones has been attributed to the release of PG or activation of sensory nerves because it could be abolished by the pretreatment with indomethacin or large neurotoxic dose of capsaicin and restored by the addition of exogenous PGE2 or CGRP, respectively. Short (5 min) ischemia of the stomach applied before prolonged ischemia-reperfusion (I/R) attenuated markedly the gastric lesions produced by this I/R and also prevented the mucosal damage provoked by necrotizing substances. This protection could be abolished by the pretreatment with non-steroidal anti-inflammatory drugs (NSAID) and was accompanied by an enhamcement of gastric mucosal COX-2 expression and activity. Exposure of gastric mucosa to single insult of acidified aspirin (ASA) causes severe mucosal damage with occurence of multiple haemorrhagic lesions but with repeated application of ASA, the attenuation of mucosal lesions is observed, despite the profound inhibition of PGE2 generation. This phenomenon called "gastric adaptation" does not appear to depend upon endogenous biosynthesis of PG but possibly involves enhanced production of growth factors increasing cell proliferation and mucosal regeneration. Unlike short lived gastroprotection by PG, NO, CGRP, mild irritants or short ischemia, gastric adaptation appears to be long-lasting phenomenon accompanied by increased resistance of the adapted mucosa to subsequent damage induced by corrosive agents.

12

Mucosal strengthening activity of central and peripheral melatonin in the mechanism of gastric defense

67%

Brzozowska I. , Ptak-Belowska A. , Pawlik M. , Bajdo R. , Drozdowicz D. , Konturek S. J. , Pawlik W. W. , Brzozowski T.

Journal of Physiology and Pharmacology. Supplement

|

2009

|

tom 60

|

nr 7

13

Role of sensory afferent nerves, lipid peroxidation and antioxidative enzymes in the carbon monoxide-induced gastroprotection against stress ulcerogensis

67%

Kwiecien S. , Magierowska K. , Magierowski M. , Surmiak M. , Hubalewska-Mazgaj M. , Pajdo R. , Sliwowski Z. , Chmura A. , Wojcik D. , Brzozowski T.

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nr 5

14

Gastroprotective and cicatrizing activity of the Ziziphus joazeiro Mart. leaf hydroalcoholic extract

67%

Brito S. M. O. , Martins A. O. B. P. B. , De Oliveira M. R. C. , Vidal C. S. , De Lacerda Neto L. J. , Ramos A. G. B. , Da Gruz L. P. , Nascimento E. A. , Da Costa J. G. M. , Coutinho H. D. M. , Quintans-Junior L. J. , De Menezes I. R. A.

Journal of Physiology and Pharmacology

|

2020

|

tom 71

|

nr 3

15

Ischemic preconditioning attenuates gastric ischemia-reperfusion injury through involvement of glucocorticoids

67%

Bobryshev P. , Bagaeva T. , Filaretova L.

Journal of Physiology and Pharmacology. Supplement

|

2009

|

tom 60

|

nr 7

16

Melatonin in gastroprotection against stress-induced acute gastric lesions and in healing of chronic gastric ulcers

67%

Konturek S. J. , Konturek P. C. , Brzozowski T.

Journal of Physiology and Pharmacology. Supplement

|

2006

|

tom 57

|

nr 5

51-66

EN

The degree of gastric damage following to exposition of the mucosa to noxious agents depends upon a balance between the factors promoting this damage and those activating the natural defense mechanisms. Recent findings, presented in this review, provide evidence that melatonin prevents the formation of acute gastric lesions induced by stress and accelerates healing of chronic gastric ulcers due to increase in the activity of nitric oxide (NO) synthase (NOS)-NO and cyclooxygenase (COX)-prostaglandin E2 (PGE2) systems resulting in the increase of mucosal blood flow and mucosal integrity. Melatonin is produced and released into the circulation by the pineal gland and, in many times larger amounts, by the gastrointestinal tract. Due to its anti-inflammatory and anti-oxidant properties, melatonin may be one of the most efficient protective factors preventing the development of acute gastric damage and accelerating healing of chronic gastric ulcers probably due to reduction in proinflammatory cytokine production, scavenging of the radical oxygen species and activation of COX-PG and NOS-NO systems as well as stimulating the afferent sensory nerves in the brain-gut axis.

17

Neural aspects of ghrelin-induced gastroprotection against mucosal injury induced by noxious agents

67%

Brzozowski T. , Konturek P. C. , Sliwowski Z. , Drozdowicz D. , Kwiecien S. , Pawlik M. , Pajdo R. , Konturek S. J. , Pawlik W. W. , Hahn E. G.

Journal of Physiology and Pharmacology. Supplement

|

2006

|

tom 57

|

nr 6

63-76

EN

Ghrelin, identified in oxyntic mucosa has been recently implicated in the control of food intake and growth hormone (GH) release but whether this hormone can influence the gastric secretion and gastric mucosal integrity have been little studied. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion in rats equipped with gastric fistula (GF) and gastric lesions induced in rats by 75% ethanol and ischemia-reperfusion (I/R) with or without vagotomy or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by H2-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. Ghrelin (5-80 µg/kg i.p. or 600-5000 ng/rat i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and I/R. These protective effects of ghrelin were accompanied by the significant rise in the gastric mucosal blood flow (GBF) and plasma ghrelin and gastrin levels. Ghrelin given i.p. or injected i.c.v. in standard doses 20 µg/kg or 5000 ng/kg, respectively, significantly attenuated the gastric mucosal damage and significantly raised the GBF. Ethanol applied i.g. in smaller concentrations (12.5% and 25%) produced a significant increase in plasma immunorective ghrelin levels and this effect was inhibited in rats receiving ethanol in higher concentrations (75% and 100%). Ghrelin-induced protection after its i.p. or i.c.v. administration and accompanying increase in the GBF were completely abolished by vagotomy and capsaicin-deactivation of sensory nerves. Concurrent treatment with CGRP added to ghrelin restored the gastroprotective and hyperemic effects of ghrelin applied i.p. or i.c.v. in rats with capsaicin denervation. We conclude that central and peripheral ghrelin exerts a potent protective and gastric secretory effects in rats exposed to ethanol and I/R, and that these actions involve vagal nerve integrity, partially depending upon afferent nerves and hyperemia mediated by sensory neuropeptides such as CGRP released from these nerves.

18

Lipopolysaccharide of Helicobacter pylori protects gastric mucosa via generation of nitric oxide

67%

Brzozowski T. , Konturek P. C. , Sliwowski Z. , Drozdowicz D. , Pajdo R. , Stachura J. , Hahn E. G. , Konturek S. J.

|

nr 4

19

Histamine in stress ulcer prophylaxis in rats

67%

Warzecha Z. , Dembinski A. , Brzozowski T. , Ceranowicz P. , Dembinski M. , Stachura J. , Konturek S. J.

|

2001

|

tom 52

|

nr 3

20

Gastroprotection by pentoxyfilline against stress-induced gastric damage. Role of lipid peroxidation, antioxidizing enzymes and proinflammatory cytokines

67%

Kwiecien S. , Brzozowski T. , Konturek P. C. , Pawlik M. W. , Pawlik W. W. , Kwiecien N. , Konturek S. J.

Journal of Physiology and Pharmacology

|

2004

|

tom 55

|

nr 2

EN

Impairment of blood perfusion in gastric mucosa results in the formation of erosions and ulcers. Nitric oxide (NO), produced via activity of NO-synthase (NOS), appears to be a one of major factors, involved in the regulation of the gastric blood flow (GBF). Inhibition of this enzyme by N-nitro-L-arginine (L-NNA) results in local decrease of NO production, reduces GBF and impairs gastric mucosal integrity, the effects that can be reversed by the pretreatment with L-arginine, the NOS substrate. However, little information is available regarding the contribution of reactive oxygen species (ROS)-induced lipid peroxidation and NO to the mechanism of gastric mucosal integrity. Therefore, the aim of our present study was to determine the action of pentoxyfilline (PTX), an inhibitor of tumor necrosis factor alpha (TNFalpha) with or without NOS inhibition by L-NNA administration in rats with water immersion and restraint stress (WRS)-induced gastric lesions . Experiments were carried out on 100 male Wistar rats. The gastric blood flow (GBF) was measured using laser Doppler flowmeter. The area of gastric lesions was determined by planimetry and the levels of proinflammatory cytokines (IL-1ß and TNFalpha) were measured by ELISA. Colorimetric assays were employed to determine gastric mucosal levels of lipid peroxidation products, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and antioxidant enzymes including superoxide dismutase (SOD) activity, as well as tissue concentration of reduced glutathione (GSH). Administration of PTX significantly attenuated the gastric lesions, induced by 3.5 h of WRS and this was accompanied by the rise in the GBF and a significant decrease in plasma proinflammatory cytokines (IL-1ß and TNFalpha) levels, as well as the reduction of lipid peroxidation. Exposure of rats to WRS supressed the SOD and GSH activities and these effects were reversed by PTX. The protective and hyperemic effects of PTX, as well as an increase in mucosal SOD activity and GSH concentration were counteracted by pretreatment with L-NNA, but restored by the pretreatment with L-arginine, a NOS substrate. We conclude that PTX exerts beneficial, gastroprotective effect against WRS-induced gastric lesions due to enhancement in gastric microcirculation, possibly mediated by the enhanced NOS activity as well as local action of NO and by the attenuation of oxidative metabolism and generation proinflammatory cytokines.