T-5224, a selective inhibitor of c-Fos/activator protein-1, attenuates lipopolysaccharide-induced liver injury in mice.

Abstract

The effect of T-5224, a selective inhibitor of c-Fos/activator protein (AP)-1, on lipopolysaccharide (LPS) induced liver injury was examined in mice. Administration of LPS (10 mg kg(-1), i.p.) markedly increased serum levels of tumor necrosis factor-alpha (TNFα), high mobility group box 1 (HMGB1), alanine aminotransferase/aspartate aminotransferase (ALT/AST), liver tissue levels of macrophage-inflammatory protein-1 alpha (MIP-1α) and monocyte chemoattractant protein-1 (MCP-1), as well as hepatic necrosis and inflammation, leading to 67 % lethality. Administration of T-5224 (300 mg kg(-1), p.o.) after intraperitoneal injection of LPS imparted appreciable protection against acute elevations in serum levels of TNFα, HMGB1, ALT/AST as well as in liver tissue levels of MIP-1α and MCP-1, and reduced the lethality (27 %). These data indicate that T-5224 ameliorates liver injury and improves survival through decreasing production of proinflammatory cytokines and chemokines in endotoxemic mice.

• Authors: Shinichiro Izuta, Masaaki Ueki, Masaki Ueno, Kahoru Nishina, Shunichi Shiozawa, Nobuhiro Maekawa
• Journal: Biotechnology letters (Biotechnol Lett) Vol. 34 Issue 12 Pg. 2175-82 (Dec 2012) ISSN: 1573-6776 [Electronic] Netherlands
• PMID: 22927112 (Publication Type: Journal Article)

Chemical References

• 3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxy-1,2-benzisoxazol-6-yl)methoxy)phenyl)propionic acid
• Benzophenones
• Cytokines
• Enzymes
• Gastrointestinal Agents
• Isoxazoles
• Lipopolysaccharides

Topics

• Animals
• Benzophenones (administration & dosage, pharmacology)
• Chemical and Drug Induced Liver Injury (prevention & control)
• Cytokines (blood)
• Disease Models, Animal
• Enzymes (blood)
• Gastrointestinal Agents (administration & dosage, pharmacology)
• Hepatitis, Animal (chemically induced, prevention & control)
• Isoxazoles (administration & dosage, pharmacology)
• Lipopolysaccharides (toxicity)
• Liver (drug effects, pathology)
• Mice
• Survival Analysis