| Role of neutrophil elastase in stress-induced gastric mucosal injury in rats. | |
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MedLine Citation:
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PMID: 9823937 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activated neutrophils play an important role in tissue injury by releasing various inflammatory mediators capable of damaging endothelial cells. To investigate whether neutrophil elastase (NE) is involved in stress-induced gastric mucosal injury, we examined the effects of 2 NE inhibitors (ONO-5046 and L-658 758) as well as nitrogen mustard-induced leukocytopenia on the formation of gastric mucosal lesions, gastric mucosal blood flow, gastric mucosal microvascular permeability, and gastric neutrophil accumulation in rats subjected to water immersion-restraint stress (WIR). Gastric mucosal injury peaked 8 hours after WIR. Gastric mucosal blood flow, as measured by laser-Doppler flow cytometry, decreased to 45% of its initial level 8 hours after WIR. Gastric mucosal microvascular permeability, evaluated by Evans blue dye leakage to the gastric mucosa, showed an increase, peaking 8 hours after WIR. Gastric accumulation of neutrophils, determined by measuring gastric myeloperoxidase activity and by histologic examination, was also significantly increased 8 hours after WIR. Both of the NE inhibitors markedly prevented the formation of gastric mucosal lesions. They also decreased the reduction in gastric mucosal blood flow seen in animals subjected to WIR while preventing increases in gastric mucosal microvascular permeability. Gastric neutrophil accumulation was significantly reduced in animals given either inhibitor 8 hours after WIR. Leukocytopenia produced effects similar to those produced by the inhibitors. Taken together, these observations strongly suggest that NE promotes stress-induced gastric mucosal injury in rats by reducing gastric mucosal blood flow and increasing neutrophil accumulation. |
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Authors:
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W Liu; K Okajima; K Murakami; N Harada; H Isobe; T Irie |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of laboratory and clinical medicine Volume: 132 ISSN: 0022-2143 ISO Abbreviation: J. Lab. Clin. Med. Publication Date: 1998 Nov |
Date Detail:
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Created Date: 1998-12-03 Completed Date: 1998-12-03 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0375375 Medline TA: J Lab Clin Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 432-9 Citation Subset: AIM; IM; S |
Affiliation:
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Department of Laboratory Medicine, Kumamoto University School of Medicine, and the Faculty of Pharmaceutical Sciences, Kumamoto University, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Capillary Permeability Cephalosporins / pharmacology Disease Models, Animal Gastric Mucosa / blood supply, enzymology*, pathology Glycine / analogs & derivatives, pharmacology Leukocyte Elastase / antagonists & inhibitors, metabolism* Leukopenia / physiopathology Male Mechlorethamine / pharmacology Neutrophils / drug effects, enzymology* Peptic Ulcer / enzymology*, etiology, pathology Peroxidase / metabolism Rats Rats, Wistar Restraint, Physical Serine Proteinase Inhibitors Specific Pathogen-Free Organisms Stress, Physiological / enzymology*, pathology Sulfonamides / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Cephalosporins; 0/Serine Proteinase Inhibitors; 0/Sulfonamides; 116507-04-1/L 658758; 127373-66-4/ONO 5046; 51-75-2/Mechlorethamine; 56-40-6/Glycine; EC 1.11.1.7/Peroxidase; EC 3.4.21.37/Leukocyte Elastase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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