Source:http://linkedlifedata.com/resource/pubmed/id/11174076
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2001-2-22
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pubmed:abstractText |
We examined the effects of ZNC-2381 (1-(4-aminophenyl)methyl-3-(3-nitrophenyl)-1,3-dihydroimidazo[4,5-b] pyridine-2-one), a new oral hepatoprotective agent, on hepatocellular caspase-3 activity and apoptosis induced by anti-mouse Fas antibody (anti-Fas ab) in mice. Oral ZNC-2381, administered at doses of 10, 30 and 100 mg/kg 1 h before inducing hepatic injury with anti-Fas ab, dose-dependently inhibited the increase in serum alanine aminotransferase (s-ALT) activity 8 h after injection of anti-Fas ab. Increases in DNA fragmentation (nucleosome assay) and caspase-3 activity in the liver 2 h after injection of anti-Fas ab were also inhibited by ZNC-2381 in a dose-dependent manner. As shown by histopathological examination, ZNC-2381 dose-dependently inhibited the appearance of TUNEL-positive apoptotic cells in the liver. Moreover, in studies in vitro, ZNC-2381 (1- 100 micromol/l) concentration-dependently inhibited increases in DNA fragmentation and caspase-3 activity caused by anti-Fas ab in isolated mouse hepatocytes. N- Acetyl-Asp-Glu-Val-Asp aldehyde (Ac-DEVD-cho), a caspase-3-specific inhibitor, inhibited hepatocellular apoptosis caused by anti-Fas ab both in vivo and in vitro, as well as the increase in s-ALT activity in vivo. These results demonstrate that orally administered ZNC-2381 inhibits hepatocellular apoptosis induced by anti-Fas ab and presents the progression of hepatic injury. We propose that the mechanism of action of ZNC-2381 may involve blockade of the signal transduction pathway (caspase-3) of apoptosis mediated by anti-Fas ab.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-(4-aminophenyl)methyl-3-(3-nitroph...,
http://linkedlifedata.com/resource/pubmed/chemical/Alanine Transaminase,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/acetyl-aspartyl-glutamyl-valyl-aspar...,
http://linkedlifedata.com/resource/pubmed/chemical/anti-Fas monoclonal antibody
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0031-7012
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2001 S. Karger AG, Basel.
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pubmed:issnType |
Print
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pubmed:volume |
62
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
80-6
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11174076-Alanine Transaminase,
pubmed-meshheading:11174076-Animals,
pubmed-meshheading:11174076-Antibodies, Monoclonal,
pubmed-meshheading:11174076-Apoptosis,
pubmed-meshheading:11174076-Caspase 3,
pubmed-meshheading:11174076-Caspases,
pubmed-meshheading:11174076-Cysteine Proteinase Inhibitors,
pubmed-meshheading:11174076-DNA Fragmentation,
pubmed-meshheading:11174076-Female,
pubmed-meshheading:11174076-Hepatocytes,
pubmed-meshheading:11174076-Male,
pubmed-meshheading:11174076-Mice,
pubmed-meshheading:11174076-Mice, Inbred BALB C,
pubmed-meshheading:11174076-Oligopeptides,
pubmed-meshheading:11174076-Pyridines
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pubmed:year |
2001
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pubmed:articleTitle |
Effects of a novel hepatoprotective drug, ZNC-2381, on fas-induced hepatocellular caspase-3 activity and apoptosis in mice.
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pubmed:affiliation |
Central Research Laboratories, Zeria Pharmaceutical Co., Kohnan-machi, Ohsato-gun, Saitama, Japan.
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pubmed:publicationType |
Journal Article
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