Metalloproteinase inhibitor prevents hepatic injury in endotoxemic mice
This study was conducted to examine of [4-( N-hydroxyamino)-2 R-isobutyl-3 S-(phenylthiomethyl)-succinyl]- l-phenylalanine- N-methylamide (GI 129471), a matrix metalloproteinase inhibitor, for its effects on increase of serum pro-inflammatory cytokine levels as well as hepatic injury in d-galactosam...
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| Veröffentlicht in: | European journal of pharmacology 1998-01, Vol.341 (1), p.105-110 |
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| container_title | European journal of pharmacology |
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| creator | Murakami, Kazuki Kobayashi, Fujio Ikegawa, Ruriko Koyama, Mamoru Shintani, Nahoko Yoshida, Tomohiro Nakamura, Norifumi Kondo, Takao |
| description | This study was conducted to examine of [4-(
N-hydroxyamino)-2
R-isobutyl-3
S-(phenylthiomethyl)-succinyl]-
l-phenylalanine-
N-methylamide (GI 129471), a matrix metalloproteinase inhibitor, for its effects on increase of serum pro-inflammatory cytokine levels as well as hepatic injury in
d-galactosamine plus lipopolysaccharide-injected mice. In vitro experiments showed that GI 129471 was able to inhibit the elevation of tumor necrosis factor-
α (TNF-
α) in LPS-stimulated human and mouse whole blood with IC
50 values of 370 nM and 260 nM, respectively. When administrated i.p. at 40 mg/kg, GI 129471 significantly reduced serum TNF-
α level but not other pro-inflammatory cytokines in
d-galactosamine plus lipopolysaccharide-injected mice. Treatment of mice with GI 129471 also reduced biochemical indices of hepatic injury to the normal level. Histopathological findings indicated that GI 129471 treatment can prevent severe centrilobular necrosis in liver. These results suggest that release of TNF-
α from lipopolysaccharide-stimulated cells is the critical step leading to hepatic injury in endotoxemia and that a matrix metalloproteinase inhibitor with an inhibitory action on this step may be a promising drug for the clinical treatment of endotoxemia accompanied by hepatic injury. |
| doi_str_mv | 10.1016/S0014-2999(97)01448-9 |
| format | Article |
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N-hydroxyamino)-2
R-isobutyl-3
S-(phenylthiomethyl)-succinyl]-
l-phenylalanine-
N-methylamide (GI 129471), a matrix metalloproteinase inhibitor, for its effects on increase of serum pro-inflammatory cytokine levels as well as hepatic injury in
d-galactosamine plus lipopolysaccharide-injected mice. In vitro experiments showed that GI 129471 was able to inhibit the elevation of tumor necrosis factor-
α (TNF-
α) in LPS-stimulated human and mouse whole blood with IC
50 values of 370 nM and 260 nM, respectively. When administrated i.p. at 40 mg/kg, GI 129471 significantly reduced serum TNF-
α level but not other pro-inflammatory cytokines in
d-galactosamine plus lipopolysaccharide-injected mice. Treatment of mice with GI 129471 also reduced biochemical indices of hepatic injury to the normal level. Histopathological findings indicated that GI 129471 treatment can prevent severe centrilobular necrosis in liver. These results suggest that release of TNF-
α from lipopolysaccharide-stimulated cells is the critical step leading to hepatic injury in endotoxemia and that a matrix metalloproteinase inhibitor with an inhibitory action on this step may be a promising drug for the clinical treatment of endotoxemia accompanied by hepatic injury.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/S0014-2999(97)01448-9</identifier><identifier>PMID: 9489862</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Animals ; Biological and medical sciences ; Digestive system ; Endotoxemia - chemically induced ; Endotoxemia - complications ; Endotoxemia - drug therapy ; GI 129471 ; Hepatic injury ; Humans ; Lipopolysaccharide ; Liver - drug effects ; Liver - injuries ; Male ; Medical sciences ; Metalloendopeptidases - antagonists & inhibitors ; Metalloproteinase inhibitor ; Mice ; Pharmacology. Drug treatments ; Phenylalanine - analogs & derivatives ; Phenylalanine - pharmacology ; Protease Inhibitors - pharmacology ; TNF- α (Tumor necrosis factor- α) ; Tumor Necrosis Factor-alpha - drug effects ; Tumor Necrosis Factor-alpha - metabolism ; Wounds and Injuries - complications ; Wounds and Injuries - drug therapy ; Wounds and Injuries - prevention & control</subject><ispartof>European journal of pharmacology, 1998-01, Vol.341 (1), p.105-110</ispartof><rights>1998 Elsevier Science B.V.</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-e77d383f5f73c8f7eb40b5ffe240ab3057775d36577997da6116406d6b877c3b3</citedby><cites>FETCH-LOGICAL-c389t-e77d383f5f73c8f7eb40b5ffe240ab3057775d36577997da6116406d6b877c3b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014299997014489$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2134151$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9489862$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Murakami, Kazuki</creatorcontrib><creatorcontrib>Kobayashi, Fujio</creatorcontrib><creatorcontrib>Ikegawa, Ruriko</creatorcontrib><creatorcontrib>Koyama, Mamoru</creatorcontrib><creatorcontrib>Shintani, Nahoko</creatorcontrib><creatorcontrib>Yoshida, Tomohiro</creatorcontrib><creatorcontrib>Nakamura, Norifumi</creatorcontrib><creatorcontrib>Kondo, Takao</creatorcontrib><title>Metalloproteinase inhibitor prevents hepatic injury in endotoxemic mice</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>This study was conducted to examine of [4-(
N-hydroxyamino)-2
R-isobutyl-3
S-(phenylthiomethyl)-succinyl]-
l-phenylalanine-
N-methylamide (GI 129471), a matrix metalloproteinase inhibitor, for its effects on increase of serum pro-inflammatory cytokine levels as well as hepatic injury in
d-galactosamine plus lipopolysaccharide-injected mice. In vitro experiments showed that GI 129471 was able to inhibit the elevation of tumor necrosis factor-
α (TNF-
α) in LPS-stimulated human and mouse whole blood with IC
50 values of 370 nM and 260 nM, respectively. When administrated i.p. at 40 mg/kg, GI 129471 significantly reduced serum TNF-
α level but not other pro-inflammatory cytokines in
d-galactosamine plus lipopolysaccharide-injected mice. Treatment of mice with GI 129471 also reduced biochemical indices of hepatic injury to the normal level. Histopathological findings indicated that GI 129471 treatment can prevent severe centrilobular necrosis in liver. These results suggest that release of TNF-
α from lipopolysaccharide-stimulated cells is the critical step leading to hepatic injury in endotoxemia and that a matrix metalloproteinase inhibitor with an inhibitory action on this step may be a promising drug for the clinical treatment of endotoxemia accompanied by hepatic injury.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Digestive system</subject><subject>Endotoxemia - chemically induced</subject><subject>Endotoxemia - complications</subject><subject>Endotoxemia - drug therapy</subject><subject>GI 129471</subject><subject>Hepatic injury</subject><subject>Humans</subject><subject>Lipopolysaccharide</subject><subject>Liver - drug effects</subject><subject>Liver - injuries</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metalloendopeptidases - antagonists & inhibitors</subject><subject>Metalloproteinase inhibitor</subject><subject>Mice</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenylalanine - analogs & derivatives</subject><subject>Phenylalanine - pharmacology</subject><subject>Protease Inhibitors - pharmacology</subject><subject>TNF- α (Tumor necrosis factor- α)</subject><subject>Tumor Necrosis Factor-alpha - drug effects</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Wounds and Injuries - complications</subject><subject>Wounds and Injuries - drug therapy</subject><subject>Wounds and Injuries - prevention & control</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM9LwzAUx4Moc07_hEEPInqoJk3bNCeRoVOYeFDPIU1fWEZ_zCQd7r8328quHh4v5Pt5yeOD0JTge4JJ_vCJMUnjhHN-y9ldOKdFzE_QmBSMx5iR5BSNj8g5unBuhTHOeJKN0IinBS_yZIzm7-BlXXdr23kwrXQQmXZpSuM7G60tbKD1LlrCWnqjQrTq7Ta0CNqq890vNOE2FFyiMy1rB1dDn6Dvl-ev2Wu8-Ji_zZ4WsaIF9zEwVtGC6kwzqgrNoExxmWkNSYplSXHGGMsqmofOOatkTkie4rzKy4IxRUs6QTeHd8PCPz04LxrjFNS1bKHrnWCc4VA0gNkBVLZzzoIWa2saabeCYLETKPYCxc6O4EzsBQoe5qbDB33ZQHWcGoyF_HrIpVOy1la2yrgjlhCakowE7PGAQZCxMWCFUwZaBZWxoLyoOvPPIn-Auo0p</recordid><startdate>19980102</startdate><enddate>19980102</enddate><creator>Murakami, Kazuki</creator><creator>Kobayashi, Fujio</creator><creator>Ikegawa, Ruriko</creator><creator>Koyama, Mamoru</creator><creator>Shintani, Nahoko</creator><creator>Yoshida, Tomohiro</creator><creator>Nakamura, Norifumi</creator><creator>Kondo, Takao</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19980102</creationdate><title>Metalloproteinase inhibitor prevents hepatic injury in endotoxemic mice</title><author>Murakami, Kazuki ; Kobayashi, Fujio ; Ikegawa, Ruriko ; Koyama, Mamoru ; Shintani, Nahoko ; Yoshida, Tomohiro ; Nakamura, Norifumi ; Kondo, Takao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-e77d383f5f73c8f7eb40b5ffe240ab3057775d36577997da6116406d6b877c3b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Digestive system</topic><topic>Endotoxemia - chemically induced</topic><topic>Endotoxemia - complications</topic><topic>Endotoxemia - drug therapy</topic><topic>GI 129471</topic><topic>Hepatic injury</topic><topic>Humans</topic><topic>Lipopolysaccharide</topic><topic>Liver - drug effects</topic><topic>Liver - injuries</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metalloendopeptidases - antagonists & inhibitors</topic><topic>Metalloproteinase inhibitor</topic><topic>Mice</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenylalanine - analogs & derivatives</topic><topic>Phenylalanine - pharmacology</topic><topic>Protease Inhibitors - pharmacology</topic><topic>TNF- α (Tumor necrosis factor- α)</topic><topic>Tumor Necrosis Factor-alpha - drug effects</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Wounds and Injuries - complications</topic><topic>Wounds and Injuries - drug therapy</topic><topic>Wounds and Injuries - prevention & control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Murakami, Kazuki</creatorcontrib><creatorcontrib>Kobayashi, Fujio</creatorcontrib><creatorcontrib>Ikegawa, Ruriko</creatorcontrib><creatorcontrib>Koyama, Mamoru</creatorcontrib><creatorcontrib>Shintani, Nahoko</creatorcontrib><creatorcontrib>Yoshida, Tomohiro</creatorcontrib><creatorcontrib>Nakamura, Norifumi</creatorcontrib><creatorcontrib>Kondo, Takao</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Murakami, Kazuki</au><au>Kobayashi, Fujio</au><au>Ikegawa, Ruriko</au><au>Koyama, Mamoru</au><au>Shintani, Nahoko</au><au>Yoshida, Tomohiro</au><au>Nakamura, Norifumi</au><au>Kondo, Takao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metalloproteinase inhibitor prevents hepatic injury in endotoxemic mice</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>1998-01-02</date><risdate>1998</risdate><volume>341</volume><issue>1</issue><spage>105</spage><epage>110</epage><pages>105-110</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>This study was conducted to examine of [4-(
N-hydroxyamino)-2
R-isobutyl-3
S-(phenylthiomethyl)-succinyl]-
l-phenylalanine-
N-methylamide (GI 129471), a matrix metalloproteinase inhibitor, for its effects on increase of serum pro-inflammatory cytokine levels as well as hepatic injury in
d-galactosamine plus lipopolysaccharide-injected mice. In vitro experiments showed that GI 129471 was able to inhibit the elevation of tumor necrosis factor-
α (TNF-
α) in LPS-stimulated human and mouse whole blood with IC
50 values of 370 nM and 260 nM, respectively. When administrated i.p. at 40 mg/kg, GI 129471 significantly reduced serum TNF-
α level but not other pro-inflammatory cytokines in
d-galactosamine plus lipopolysaccharide-injected mice. Treatment of mice with GI 129471 also reduced biochemical indices of hepatic injury to the normal level. Histopathological findings indicated that GI 129471 treatment can prevent severe centrilobular necrosis in liver. These results suggest that release of TNF-
α from lipopolysaccharide-stimulated cells is the critical step leading to hepatic injury in endotoxemia and that a matrix metalloproteinase inhibitor with an inhibitory action on this step may be a promising drug for the clinical treatment of endotoxemia accompanied by hepatic injury.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>9489862</pmid><doi>10.1016/S0014-2999(97)01448-9</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-2999 |
| ispartof | European journal of pharmacology, 1998-01, Vol.341 (1), p.105-110 |
| issn | 0014-2999 1879-0712 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_79707973 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Biological and medical sciences Digestive system Endotoxemia - chemically induced Endotoxemia - complications Endotoxemia - drug therapy GI 129471 Hepatic injury Humans Lipopolysaccharide Liver - drug effects Liver - injuries Male Medical sciences Metalloendopeptidases - antagonists & inhibitors Metalloproteinase inhibitor Mice Pharmacology. Drug treatments Phenylalanine - analogs & derivatives Phenylalanine - pharmacology Protease Inhibitors - pharmacology TNF- α (Tumor necrosis factor- α) Tumor Necrosis Factor-alpha - drug effects Tumor Necrosis Factor-alpha - metabolism Wounds and Injuries - complications Wounds and Injuries - drug therapy Wounds and Injuries - prevention & control |
| title | Metalloproteinase inhibitor prevents hepatic injury in endotoxemic mice |
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