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Modulation of hepatotoxicity by macrophages in the liver
Author(s) -
Shiratori Yasushi,
Kawase Tateo,
Shiina Shuichiro,
Okano Ken'Ichi,
Sugimoto Tsuneaki,
Teraoka Hitoshi,
Matano Sunao,
Matsumoto Kazunori,
Kamii Kazuo
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.1840080420
Subject(s) - galactosamine , superoxide dismutase , chemistry , liver injury , superoxide , medicine , biochemistry , endocrinology , antioxidant , enzyme , glucosamine
In an attempt to elucidate the role of hepatic macrophages in liver injury, we investigated galactosamine‐treated rats (500 mg per kg body weight). The rats received an i.v. injection of latex particles (2 × 10 9 particles per animal) prior to (latex‐galactosamine) or 12 to 16 hr subsequent to the galactosamine treatment (galactosamine‐latex). Effect of superoxide dismutase on hepatic injury induced by galactosamine or galactosamine‐latex treatment was also examined. Oxygen‐derived free radical‐generating capacity of isolated hepatic macrophages was measured as chemiluminescence with the stimulation of phorbol myristate acetate or latex particles. As compared with normal rats, chemiluminescence of hepatic macrophages from galactosamine‐treated rats was 5‐ to 10‐fold enhanced 12 hr following galactosamine treatment and remained elevated for 48 hr. Chemiluminescence of the latex particle‐pretreated macrophages in the liver was markedly suppressed even following the galactosamine treatment (p < 0.01). Compared to galactosamine‐treated rats, both lipid peroxide level in the liver tissue and AST and ALT concentration in serum were significantly decreased in the latex‐galactosamine‐treated rats < p < 0.01) and increased in the galactosamine‐latex‐treated rats (p < 0.01). Furthermore, superoxide dismutase supplementation protected against liver injury induced by the galactosamine‐latex treatment. From these results, pretreatment with latex particles suppressed the free radical‐generating capacity of hepatic macrophages and protected against hepatic injury induced by galactosamine. In contrast, injection of latex particles after galactosamine treatment aggravated hepatic injury, which was prevented by superoxide dismutase. These data suggest that liver injury induced by galactosamine is modulated by oxygen‐derived free radicals from hepatic macrophages.