Gastric adaptation to injury by repeated doses of aspirin strengthens mucosal defence against subsequent exposure to various strong irritants in rats.

Brzozowski, Tomasz; Konturek, Peter C.; Konturek, S J; Ernst, Hans; Stachura, Jerzy; Hahn, Eckhart G.

doi:10.1136/gut.37.6.749

Cited by 30 publications

(31 citation statements)

References 34 publications

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“…or i.g.) or were treated repeatedly with HP LPS for 4 consecutive days, as described in detail in our previous studies with aspirin- and ammonia-induced gastric adaptation [18, 19, 20]. Briefly, one group of rats (n = 8) received HP LPS (1 ml/rat) and was sacrificed 2 h later (LPS once).…”

Section: Methodsmentioning

confidence: 99%

Enhanced Resistance of Gastric Mucosa to Damaging Agents in the Rat Stomach Adapted to Helicobacter pylori Lipopolysaccharide

Brzozowski

Konturek²,

Moran³

et al. 2003

Digestion

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Background and Aim: Lipopolysaccharide (LPS) has been proposed to act as one of numerous virulence factors in the Helicobacter pylori (HP)-infected stomach. However, little is known as to whether the gastric mucosa can withstand the repeated LPS insult, and how the possible adaptation to this endotoxin influences the damage induced by strong irritants. We determined the effect of a single or repeated parenteral administration of LPS obtained from HP on acute gastric lesions induced by intragastric application of 100% ethanol (1.5 ml) and by water immersion and restraint stress (WRS). Methods: The area of the gastric lesions was measured by planimetry, mucosal gastric blood flow (GBF) was determined by H₂ gas clearance, and gastric luminal content was collected for the determination of luminal NO₂^–/NO₃^– levels by the Griess reaction. Biopsy samples were taken for the measurement of prostaglandin (PG) E₂ by radioimmunoassay and mucosal expression of constitutive and inducible nitric oxide synthase (cNOS and iNOS), constitutive (COX-1) and inducible cyclooxygenase (COX-2), heat shock protein 70 (HSP 70) mRNA and protein were analyzed by RT-PCR and Western blot. Results:HP LPS (1 mg/kg i.p.) injected once or 5 times produced negligible macroscopic injury and failed to influence GBF significantly compared to the injuries recorded in vehicle-controlled rats. Single and repeated (5 times) administration of HP LPS significantly reduced ethanol- and WRS-induced lesions, these protective effects were accompanied by a rise in GBF and excessive luminal release of NO. The suppression of NOS activity by L-NAME (20 mg/kg i.p.), a nonspecific NOS inhibitor, or L- (30 mg/kg i.g.), a specific iNOS inhibitor, and of COX-2 activity by NS-398 reversed the protective and hyperemic effects of single or repeated LPS administrations against ethanol and WRS damage and the accompanying rise in NO and PGE₂ production. These effects of L-NAME were significantly antagonized by the addition of L-arginine, a substrate for NO synthesis. The signals for cNOS, COX-1 and HSP 70 mRNA were detected by RT-PCR in the vehicle-treated gastric mucosa, whereas gene and protein expression of iNOS, COX-2 and HSP 70 mRNA were significantly increased only in rats treated with 1 or 5 applications of HP LPS. Conclusions: Repeated injections of HP LPS enhance gastric mucosal resistance to the mucosal damage induced by ethanol and WRS via a mechanism involving mucosal overexpression of iNOS, COX-2 and HSP 70 with subsequent excessive production of NO and PGE₂.

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Section: Methodsmentioning

confidence: 99%

Enhanced Resistance of Gastric Mucosa to Damaging Agents in the Rat Stomach Adapted to Helicobacter pylori Lipopolysaccharide

Brzozowski

Konturek²,

Moran³

et al. 2003

Digestion

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“…As mentioned above, to evaluate the effect of WE of Hp strains on GBF, the abdomen was opened under ether anesthesia and the stomach was exposed to assess the GBF in the ulcer margin and ulcer crater (well seen from the serosal site) and in the adjacent intact mucosa using the H 2 -gas clearance technique as described previously [24]. For GBF measurement, the double electrodes of an electrolytic regional blood flow meter (Biotechnical Science, Model RBF-2, Osaka, Japan) were inserted into the mucosa.…”

Section: Methodsmentioning

confidence: 99%

Water Extracts of Helicobacter pylori Delay Healing of Chronic Gastric Ulcers in Rats: Role of Cytokines and Gastrin-Somatostatin Link

Brzozowski

Konturek

et al. 1999

Digestion

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Background: Helicobacter pylori (Hp) is considered as a major risk factor of peptic ulcer, but the pathogenic mechanism of its action has not been fully explained. Aims: This study was designed: (1) to compare the ulcer healing effects of water extract (WE) obtained from type-I cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) expressing Hp and from type-II CagA- and VacA-negative Hp strain with those of vehicle (saline), and (2) to determine the alterations in gastric secretion, gastric blood flow (GBF) and expression of Hp-related cytokines during the ulcer healing in rats treated with toxigenic (type-I) and non-toxigenic (type-II) Hp-derived WE. Methods: Gastric ulcers were produced by serosal application of acetic acid in rats with or without gastric fistula treated with vehicle (saline) or WE originating from type-I or type-II Hp administered intragastrically on days 1, 3, 5 and 7 upon ulcer induction. On days 3, 9 and 15, animals were lightly anesthetized with ether, the abdomen was opened and the GBF was measured by the H₂-gas clearance technique in the ulcer area and non-ulcerated mucosa. Venous blood was withdrawn for the measurement of plasma cytokine (IL-1β and TNFα) levels and plasma and gastric contents were also collected for gastrin and somatostatin determination by specific radioimmunoassay. Results: Gastric ulcers healed gradually in vehicle-treated controls and the ulcer area on days 3, 9 and 15 was reduced by 12, 43 and 92%, respectively. In rats treated with WE of type-I Hp, ulcer healing was significantly delayed, and gastritis and infiltration of ulcerated gastric mucosa with inflammatory cells were observed histologically. The prolongation of ulcer healing by WE of both Hp strains was accompanied by a marked fall in the GBF at the ulcer margin and transient hyposecretion especially in rats given WE of type-I Hp strain. On day 15 of ulcer healing, the plasma concentration of IL-1β and TNFα was negligible in vehicle control rats, but it was significantly elevated particularly in rats treated with WE of type-I Hp. RT-PCR analysis revealed that mucosal expression of IL-1β and TNFα mRNA was significantly upregulated in the gastric mucosa of rats treated with either toxigenic or non-toxigenic Hp WE. The plasma gastrin level was significantly higher and the luminal concentration of somatostatin was significantly lower in rats treated with Hp-WE than in vehicle-treated controls and these alterations were more pronounced in rats treated with WE type-I than type-II Hp. Conclusions: WE of toxigenic Hp strain delays ulcer healing due to the reduction in the gastric microcirculation at the ulcer margin, the overexpression of inflammatory cytokines and the impairment of the gastrin-somatostatin link.

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“…GMBF was measured using hydrogen gas clearance technique [18]. The clearance curve of tissue hydrogen was used to calculate the volume of blood flow (ml/min/100g).…”

Section: Gastric Secretionmentioning

confidence: 99%

Aspirin Can Elicit The Recurrence of Gastric Ulcer Induced with Acetic Acid in Rats

Guo-zhong

Huang²,

Yin³

et al. 2007

Cell Physiol Biochem

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This study was supported by grants of New Ideas Capability for Backbone Teachers in Universities of Heilongjiang and of Scientific Research foundation in Qiqihar Medical College. Background/ Aims: Ulcer recurrence and poor healing may be critically important to the development of serious gastrointestinal complications in patients with long-term non-steroid anti-inflammatory drugs (NSAIDs). The present study is to investigate the effects of aspirin on ulcer recurrence and healing quality and to explore the mechanism. Methods: Gastric ulcers were induced with acetic acid in rats; aspirin was administrated by gavage from day 25 to day 54 after ulcer induction. The gastric juice volume, pH, gastric mucus, gastric mucosal blood flow (GMBF) and prostaglandin E₂ (PGE₂) were measured. The mRNA transcription of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were analyzed with RT-PCR and protein expression with Western blot. Results: The gastric juice volume was significantly increased in aspirin group compared with those of fasting or saline control groups (P<0.01); while the pH, mucus, GMBF and PGE₂ were significantly decreased in aspirin treated rats compared with those of other two groups (P<0.01). COX-2, evaluated with mRNA and protein expression, was significantly augmented in aspirin group compared with others. The quality of ulcer healing (QOUH) in Aspirin group was poorer than that of fasting or saline control groups. Conclusions: Aspirin enhance the recurrence of gastric ulcer. The inhibition of cycloxygenase, mucus secretion and mucosal blood flow may be involved. Aspirin also impair the quality of ulcer healing.

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Gastric adaptation to injury by repeated doses of aspirin strengthens mucosal defence against subsequent exposure to various strong irritants in rats.

Cited by 30 publications

References 34 publications

Enhanced Resistance of Gastric Mucosa to Damaging Agents in the Rat Stomach Adapted to <i>Helicobacter pylori</i> Lipopolysaccharide

Enhanced Resistance of Gastric Mucosa to Damaging Agents in the Rat Stomach Adapted to <i>Helicobacter pylori</i> Lipopolysaccharide

Water Extracts of <i>Helicobacter pylori</i> Delay Healing of Chronic Gastric Ulcers in Rats: Role of Cytokines and Gastrin-Somatostatin Link

Aspirin Can Elicit The Recurrence of Gastric Ulcer Induced with Acetic Acid in Rats

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