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Cooperative effect of biliverdin and carbon monoxide on survival of mice in immune‐mediated liver injury
Author(s) -
Sass Gabriele,
Seyfried Stefan,
Parreira Soares Miguel,
Yamashita Kenichiro,
Kaczmarek Elzbieta,
Neuhuber Winfried L.,
Tiegs Gisa
Publication year - 2004
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20450
Subject(s) - biliverdin , heme oxygenase , liver injury , tumor necrosis factor alpha , heme , lipopolysaccharide , hepatology , cytokine , apoptosis , chemistry , pharmacology , immunology , medicine , biochemistry , enzyme
Abstract Induction of the heme‐degrading enzyme heme oxygenase‐1 (HO‐1) has been shown to be beneficial in terms of improvement of liver allograft survival and prevention of CD95‐mediated apoptosis in the liver. In the present study, we investigated the effects of HO‐1, and its products carbon monoxide (CO), biliverdin (BV), and iron/ferritin, in a mouse model of inflammatory liver damage inducible by lipopolysaccharide (LPS) in mice sensitized with the hepatocyte‐specific transcription inhibitor D ‐galactosamine (GalN). Our results show that HO‐1 induction by cobalt‐protoporphyrin‐IX (CoPP) reduced cytokine expression, protected mice from liver injury, and prolonged survival. While in contrast to ferritin overexpression, single administration of the CO donor methylene chloride (MC) or of BV also protected mice from liver damage, only coadministration of both HO products prolonged survival and reduced the expression of cytokines, e.g. , tumor necrosis factor (TNF) and interferon γ (IFN‐γ). In conclusion , HO‐1–induced prolongation of survival, but not the protection from liver damage, seems to be dependent on down‐regulation of cytokine synthesis. (H EPATOLOGY 2004;40:1128–1135.)