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Activation of liver macrophages following phenobarbital treatment of rats
Author(s) -
Laskin Debra L.,
Robertson Fredika M.,
Pilaro Anne M.,
Laskin Jeffrey D.
Publication year - 1988
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.1840080512
Subject(s) - phenobarbital , inducer , phagocytosis , cytochrome , macrophage , chemistry , biotransformation , liver cytology , pharmacology , immunology , biology , biochemistry , in vitro , enzyme , liver metabolism , gene
Phenobarbital is a potent inducer of hepatic cytochrome P‐450 and is a tumor promoter in the two‐stage model of liver carcinogenesis. In the present studies, we show that phenobarbital also induces an accumulation of activated macrophages in the livers of treated rats. These macrophages are larger and more stellate than resident Kupffer cells and are highly vacuolated. In addition, macrophages isolated from livers of phenobarbital‐treated rats display increased phagocytosis of sheep red blood cells, chemotaxis toward the complement fragment C5a and enhanced production of hydrogen peroxide. Biologically active mediators released by activated macrophages have been implicated in tumor promotion as well as in the regulation of cytochrome P‐450‐mediated drug biotransformation. We propose that the activated macrophages that accumulate in the liver following phenobarbital treatment may contribute, at least in part, to the biological responses to this drug.