Therapeutic administration of Y-40138, a multiple cytokine modulator, inhibits concanavalin A-induced hepatitis in mice.

Abstract	Concanavalin A-induced hepatitis is often used as a model of liver injury. In this model, plasma tumor necrosis factor-alpha (TNF-alpha) level increased in concanavalin A-injected mice. Prophylactic treatment with Y-40138, N-[1-(4-[4-(pyrimidin-2-yl)piperazin-1-yl]methyl phenyl)cyclopropyl] acetamide.HCl, significantly suppressed the increase in plasma TNF-alpha level. In this study, we compared the effect of Y-40138 with those of pentoxifylline and anti-TNF-alpha antibody on concanavalin A-induced hepatitis. Prophylactic treatment with pentoxifylline, anti-TNF-alpha antibody and Y-40138 reduced plasma alanine aminotransferase level. Therapeutic treatment with Y-40138 significantly reduced plasma alanine aminotransferase level, but pentoxifylline and anti-TNF-alpha antibody did not. Therapeutic treatment with Y-40138 significantly reduced plasma interferon-gamma (IFN-gamma) and monokine induced by interferon-gamma levels. From these results, Y-40138 may be expected as a new class of therapeutic drug for treatment of TNF-alpha, IFN-gamma and/or chemokine-related liver diseases such as alcoholic liver disease.
Authors	Tetsuko Fukuda, Akira Mogami, Masao Hisadome, Hirotsugu Komatsu
Journal	European journal of pharmacology (Eur J Pharmacol) Vol. 523 Issue 1-3 Pg. 137-42 (Oct 31 2005) ISSN: 0014-2999 [Print] Netherlands
PMID	16236280 (Publication Type: Comparative Study, Journal Article)
Chemical References	Acetamides Antibodies Chemokines, CXC Cytokines Piperazines Tumor Necrosis Factor-alpha Y 39041 Concanavalin A Interferon-gamma Alanine Transaminase Pentoxifylline
Topics	Acetamides (administration & dosage, therapeutic use) Alanine Transaminase (blood) Animals Antibodies (administration & dosage, therapeutic use) Chemical and Drug Induced Liver Injury (blood, etiology, prevention & control) Chemokines, CXC (blood) Concanavalin A (adverse effects) Cytokines (blood) Disease Models, Animal Female Interferon-gamma (blood) Mice Mice, Inbred BALB C Pentoxifylline (administration & dosage, therapeutic use) Piperazines (administration & dosage, therapeutic use) Premedication Time Factors Tumor Necrosis Factor-alpha (analysis, immunology)

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