کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9244002 | 1209898 | 2005 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of Hydrogen Sulfide Generation Contributes to Gastric Injury Caused by Anti-Inflammatory Nonsteroidal Drugs
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
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![عکس صفحه اول مقاله: Inhibition of Hydrogen Sulfide Generation Contributes to Gastric Injury Caused by Anti-Inflammatory Nonsteroidal Drugs Inhibition of Hydrogen Sulfide Generation Contributes to Gastric Injury Caused by Anti-Inflammatory Nonsteroidal Drugs](/preview/png/9244002.png)
چکیده انگلیسی
Background & Aims: Hydrogen sulfide (H2S), an endogenous gaseous mediator that causes vasodilation, is generated in mammalian tissues by cystathionine β-synthase (CBS) and cystathionine-γ-lyase (CSE). Here, we have investigated the role of H2S in a rodent model of nonsteroidal anti-inflammatory drug (NSAID) gastropathy. Methods: Rats were given acetyl salycilic acid (ASA) or an NSAID alone or in combination with NaHS, an H2S donor, and killed 3 hours later. Gastric blood flow was measured by laser-Doppler flowmetry, whereas intravital microscopy was used to quantify adhesion of leukocytes to mesenteric postcapillary endothelium. Results: At a dose of 100 μmol/kg, NaHS attenuated by 60%-70% the gastric mucosal injury, and tumor necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, and lymphocyte function-associated antigen (LFA)-1 mRNA up-regulation induced by NSAIDs (P < .05) NaHS administration prevented the associated reduction of gastric mucosal blood flow (P < .05) and reduced ASA-induced leukocyte adherence in mesenteric venules. NaHS did not affect suppression of prostaglandin E2 (PGE2) synthesis by NSAIDs. Glibenclamide, a KATP channel inhibitor, and DL-propargylglycine, a CSE inhibitor, exacerbated, whereas pinacidil, a KATP opener, attenuated gastric injury caused by ASA. Exposure to NSAIDs reduced H2S formation and CSE expression (mRNA and protein) and activity by 60%-70%. By promoter deletion and mutation analysis, an Sp1 consensus site was identified in the CSE promoter. Exposure to NSAIDs inhibits Sp1 binding to its promoter and abrogates CSE expression in HEK-293 cells transfected with a vector containing the core CSE promoter. Exposure to NSAIDs inhibits Sp1 and ERK phosphorylation. Conclusions: These data establish a physiologic role for H2S in regulating the gastric microcirculation and identify CSE as a novel target for ASA/NSAIDs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 129, Issue 4, October 2005, Pages 1210-1224
Journal: Gastroenterology - Volume 129, Issue 4, October 2005, Pages 1210-1224
نویسندگان
Stefano Fiorucci, Elisabetta Antonelli, Eleonora Distrutti, Giovanni Rizzo, Andrea Mencarelli, Stefano Orlandi, Renata Zanardo, Barbara Renga, Moses Di Sante, Antonio Morelli, Giuseppe Cirino, John L. Wallace,