| N2733, 1-[3-(3-pyridyl)-acryloyl]-2-pyrrolidinone hydrochloride inhibits LPS-induced TNF-alpha production and improves survival in endotoxemic mice. | |
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MedLine Citation:
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PMID: 9972238 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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N2733, 1-[3-(3-pyridyl)-acryloyl]-2-pyrrolidinone hydrochloride, was examined for its effect on TNF-alpha production by human myeloid THP-1 cells stimulated with lipopolysaccharide (LPS). N2733 inhibited LPS-induced release of TNF-alpha from THP-1 cells with an IC50 of 11 microM. N2733 did not affect the cell viability at the concentration of 50 microM or 100 microM. This indicates that N2733 is a potent inhibitor for TNF-alpha production without severe cytotoxicity. N2733 was also studied in two murine endotoxin shock models induced with LPS. One model was DBA/2 mice injected with LPS (5.6 mg/kg, i.v.), which increased the serum level of TNF-alpha within 1 hr. Treatment of these mice with N2733 (100 mg/kg x 2, i.p.) decreased the serum level of TNF-alpha significantly. Another model was DBA/2 mice induced with LPS (30 mg/kg, i.v.), which reduced the survival rate to 30% during 7 days. Administrations of 30 mg/kg and 100 mg/kg N2733 (i.v.) restored the survival rates to 60% and 90% respectively. Our data demonstrate that N2733 inhibits LPS-induced TNF-alpha production, and this response is associated with an improvement in the survival rate of endotoxemic mice. |
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Authors:
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K Katsuyama; R Kojima; S Yokoyama; M Yanai; N Sueda; M Sugita; K Momose; H Yamada |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Bioscience, biotechnology, and biochemistry Volume: 62 ISSN: 0916-8451 ISO Abbreviation: Biosci. Biotechnol. Biochem. Publication Date: 1998 Nov |
Date Detail:
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Created Date: 1999-03-22 Completed Date: 1999-03-22 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 9205717 Medline TA: Biosci Biotechnol Biochem Country: JAPAN |
Other Details:
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Languages: eng Pagination: 2177-81 Citation Subset: IM |
Affiliation:
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Pharmaceutical Research Center, Nisshin Flour Milling Co., Ltd., Saitama, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Dose-Response Relationship, Drug Endotoxemia / drug therapy* Female Humans Lipopolysaccharides / antagonists & inhibitors* Mice Mice, Inbred DBA Protein Synthesis Inhibitors / therapeutic use* Pyrrolidinones / therapeutic use* Survival Rate Tumor Necrosis Factor-alpha / biosynthesis* |
| Chemical | |
Reg. No./Substance:
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0/1-(trans-3-(2-pyridyl)acryloyl)-2-pyrrolidinone; 0/Lipopolysaccharides; 0/Protein Synthesis Inhibitors; 0/Pyrrolidinones; 0/Tumor Necrosis Factor-alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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