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YH439, a Hepatoprotective Agent, Suppresses Cytokines and Nitric Oxide Production in LPS-primed Rats Administered with CCI4
YAKHAK HOEJI 1999;43(2):198-207
Published online April 27, 1999
© 1999 The Pharmaceutical Society of Korea.

김연숙(Young Sook Kim);이종욱(Jong Wook Lee);김낙두(Nak Doo Kim)
Abstract
The aim of the present investigation was to examine whether YH439, a hepatoprotective agent, exerts protective effect against hepatotoxicity and reduces the production of cytokines and NO in lipopolysaccharide (LPS)-primed rats with carbon tetracholride (CCl4). Administration of LPS following a single dose of CCl4 injection resulted in remarkable elevations of the serum TNFalpha, IL-1 beta and IL-6 level. The serum NO level was moderately elevated and severe liver damage was evidenced by increases in serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities. YH439 decreased the levels of TNF, IL-1 beta, IL-6, ALT, SDH as well as NO in the serum elevated by CCl4+LPS in a dose-dependent manner. Inducible nitric oxide synthase (iNOS) level was decreased in the liver of rats treated with YH439. The increased iNOS activity induced by LPS and interferon-gamma was signficantly decreased in RAW 264.7 cells by YH439 treatment. YH439 increased the GSH level decreased by CCl4+LPS and suppressed the ratio of GSSG/GSH. The reduction of hepatotoxicity by YH439 may be associated with the decrease in the production of cytokines as well as suppression of iNOS protein in conjunction with an increase in the GSH level.
Keywords : Tumor necrosis factor 2;interleukin-1β;interleukin-6;nitric oxide;hepatoprotective agent;glutathione;inducible nitric oxide synthase.


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