Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice

Souza, Marcellus H.; Lemos, Henrique; Oliveira, Ricardo Brandt de; Cunha, Fernando

doi:10.1136/gut.2002.012930

Cited by 74 publications

(62 citation statements)

References 36 publications

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“…However, even after 7 days, the autohealing was partial. The MPO activity, a marker of neutrophil aggregation at the site of inflammation frequently increases in ulcerated condition and reduces with the healing process (Souza et al, 2004). In consonance with this, we also found that ulceration increased the MPO activity up to the 4th day, followed by its gradual reduction on the 7th day (Fig.…”

Section: Discussionsupporting

confidence: 73%

Improved Antiulcer and Anticancer Properties of a trans-Resveratrol Analog in Mice

Guha¹,

Dey²,

Sarkar³

et al. 2008

J Pharmacol Exp Ther

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Despite its potential, use of trans-resveratrol as an anticancer drug is severely constrained because of its tendency to prolong gastric ulceration. We found that in addition to delaying ulcer healing, trans-resveratrol also aggravated acute gastric ulceration induced by the nonsteroidal anti-inflammatory drugs by reducing the synthesis of prostaglandin (PG) E 2 via a specific inhibition of cyclooxygenase (COX)-1 that also hampered angiogenesis. However, for the first time, we showed that the 3Ј-5Ј-hydroxylated congener [(E)-HST-1] of trans-resveratrol, synthesized in multigram scale, exerted potential chemotherapeutic property but was nonulcerogenic in nature, rather moderately accelerated healing of indomethacin-induced gastric ulceration. HST-1 did not suppress COX-1, COX-2 expression, and PGE 2 synthesis but reduced the level of inflammatory myeloperoxidase (MPO) activity. The healing was augmented primarily through the nitric oxide synthase (NOS)-dependent pathway. HST-1 treatment induced endothelial NOS (eNOS) expression and reduced inducible NOS (iNOS), resulting in increased eNOS/iNOS ratio. The selective iNOS inhibitor [L-N 6 -(1-iminoethyl) lysine hydrochloride] and nonselective NOS inhibitor (N -nitro-L-arginine methyl ester) treatment revealed that eNOS could be the probable molecular switch to accelerate the indomethacin-induced ulcer healing in HST-1-treated mice. Furthermore, the anticancer effect of HST-1 on U937 and K562 leukemia cell lines was found to be significantly better than that of trans-resveratrol. Overall, these established HST-1 as a potentially better anticancer compound than trans-resveratrol, considering it is devoid of any ulcerogenic side effects. In conclusion, for the first time, we showed that a novel analog of trans-resveratrol, HST-1, was devoid of ulcerogenic adversative effects of trans-resveratrol but retained potentially better anticancer property.

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Section: Discussionsupporting

confidence: 73%

Improved Antiulcer and Anticancer Properties of a trans-Resveratrol Analog in Mice

Guha¹,

Dey²,

Sarkar³

et al. 2008

J Pharmacol Exp Ther

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“…Several studies have demonstrated the importance of endogenous NO in the protection of gastric mucosa (Kim and Kim, 1998;Tanaka et al, 2001;Whittle et al, 1990). Also endothelial NO plays an important role in the modulation of gastric mucosal integrity by interacting with sensory neuropeptides (Whittle et al, 1990;Tepperman and Whittle, 1992), reducing neutrophil adhesion and increasing gastric blood flow and mucus secretion (Souza et al, 2004). In the present study, alcohol significantly reduced gastric mucosal NO level with increase mucosal injury compared to control group.…”

Section: Discussionsupporting

confidence: 54%

Gastroprotective effects of Stachys Lavandulifolia extract on experimental gastric ulcer

Nabavizadeh¹

2011

Afr. J. Pharm. Pharmacol.

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Several studies have used Stachys Lavandulifolia vahl (S. lavandulifolia) as medicinal plant in Iranian folk medicine. The present investigation is designed to elucidate therapeutic and preventive effects of S. lavandulifolia extract on gastric acid and pepsin secretions in experimental gastric ulcer. Thirty two Wistar male rats were used to study therapeutic and preventive effects of S. lavandulifolia extract on alcohol-induced gastric ulcer. Animals were equally (n=8) divided into 4 groups: (I) Control (II) Alcohol (1 ml/200 g/bw) to induce gastric ulcer (III) Alcohol/Lvandu (100 mg/kg bw/daily, S. lavandulifolia extract was given for two weeks post alcohol administration) and (IV) Lvandu/alcohol (S. lavandulifolia extract was given for two weeks before alcohol administration). Ulcer index, gastric acid and pepsin secretions was measured. Ulcer index was significantly decreased in alcohol/Lvandu than Alcohol group. Also gastric acid and pepsin secretions, and gastric tissue's NO metabolites level were significantly lower in alcohol and Lvandu/alcohol groups than control (p<0/05). But changes in gastric acid and pepsin secretions have not been noticeable in alcohol/Lvandu group than control. The results of this study show that S. lavandulifolia extract protected gastric mucosa from alcohol-induced gastric ulcer. This gastroprotection may mediate via gastric mucosal nitric oxide production.

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“…Mucosal blood flow is essential to maintain gastric mucosal integrity; hence increased blood flow would reduce the risk of lesion by NSAID treatment. Thus, an increase in gastric blood flow resulting from H 2 S donation could primarily prevent any initial mucosal lesion by reducing the production of local inflammatory mediators, consequently reducing leukocyte to endothelium adhesion, an event essential to the progression of gastric tissue lesion (46). Reinforcing this explanation, NO synthase inhibitors that improve neutrophil migration induced by different stimuli (27) have been shown to enhanced the NSAID-induced gastric lesion via a reduction of mucosal blood flow (47,48).…”

Section: Discussionmentioning

confidence: 87%

Hydrogen Sulfide Augments Neutrophil Migration through Enhancement of Adhesion Molecule Expression and Prevention of CXCR2 Internalization: Role of ATP-Sensitive Potassium Channels

Dal-Secco¹,

Cunha²,

Freitas³

et al. 2008

The Journal of Immunology

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In this study, we have addressed the role of H2S in modulating neutrophil migration in either innate (LPS-challenged naive mice) or adaptive (methylated BSA (mBSA)-challenged immunized mice) immune responses. Treatment of mice with H2S synthesis inhibitors, dl-propargylglycine (PAG) or β-cyanoalanine, reduced neutrophil migration induced by LPS or methylated BSA (mBSA) into the peritoneal cavity and by mBSA into the femur/tibial joint of immunized mice. This effect was associated with decreased leukocyte rolling, adhesion, and P-selectin and ICAM-1 expression on endothelium. Predictably, treatment of animals with the H2S donors, NaHS or Lawesson’s reagent, enhanced these parameters. Moreover, the NaHS enhancement of neutrophil migration was not observed in ICAM-1-deficient mice. Neither PAG nor NaHS treatment changed LPS-induced CD18 expression on neutrophils, nor did the LPS- and mBSA-induced release of neutrophil chemoattractant mediators TNF-α, keratinocyte-derived chemokine, and LTB4. Furthermore, in vitro MIP-2-induced neutrophil chemotaxis was inhibited by PAG and enhanced by NaHS treatments. Accordingly, MIP-2-induced CXCR2 internalization was enhanced by PAG and inhibited by NaHS treatments. Moreover, NaHS prevented MIP-2-induced CXCR2 desensitization. The PAG and NaHS effects correlated, respectively, with the enhancement and inhibition of MIP-2-induced G protein-coupled receptor kinase 2 expression. The effects of NaHS on neutrophil migration both in vivo and in vitro, together with CXCR2 internalization and G protein-coupled receptor kinase 2 expression were prevented by the ATP-sensitive potassium (KATP+) channel blocker, glybenclamide. Conversely, diazoxide, a KATP+ channel opener, increased neutrophil migration in vivo. Together, our data suggest that during the inflammatory response, H2S augments neutrophil adhesion and locomotion, by a mechanism dependent on KATP+ channels.

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Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice

Cited by 74 publications

References 36 publications

Improved Antiulcer and Anticancer Properties of a trans-Resveratrol Analog in Mice

Improved Antiulcer and Anticancer Properties of a trans-Resveratrol Analog in Mice

Gastroprotective effects of Stachys Lavandulifolia extract on experimental gastric ulcer

Hydrogen Sulfide Augments Neutrophil Migration through Enhancement of Adhesion Molecule Expression and Prevention of CXCR2 Internalization: Role of ATP-Sensitive Potassium Channels

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