Role of Ca2+ on endotoxin-sensitivity by galactosamine challenge: lipid peroxide formation and hepatotoxicity in zymosan-primed mice.
This study was investigated to clarify the role of intracellular Ca2+ following endotoxin treatment (1 mg/kg, intraperitoneally) to D-galactosamine-sensitized mice (400 mg/kg, intraperitoneally), and to observe lipid peroxide levels, an index of hepatotoxicity, in endotoxin/galactosamine (Ga1N)-challenged mice under activation of macrophages, especially Kupffer cells, by zymosan. The liver lipid peroxide level and serum glutamic pyruvic transminase activity in mice 18 hr after administration of endotoxin/Ga1N were markedly higher than those in mice treated only with endotoxin. In spite of an increase in lipid peroxide formation, there was little or no effect of Ga1N administration on xanthine oxidase and superoxide dismutase activities in mice given endotoxin. However, the injection of verapamil (10 mg/kg, subcutaneously) markedly decreased lipid peroxide levels in liver of endotoxin/Ga1N-injected mice. In the mice given a Ca(2+)-deficient diet, lipid peroxide level in liver after endotoxin/Ga1N injection was markedly decreased compared to that in mice fed a normal diet. Administration of dexamethasone (200 micrograms/kg, intraperitoneally) in mice 1 hr before treatment with endotoxin/Ga1N did not induce lipid peroxide formation. Administration of endotoxin to Ga1N-treated mice resulted in a higher level of liver cytosolic free Ca2+ ([Ca2+]i) than that in endotoxin-treated mice. On the other hand, Ca(2+)-ATPase activity in liver plasma membrane in the endotoxin/Ga1N-treated mice was markedly decreased as compared with endotoxin alone. On the contrary, the Ca(2+)-ATPase activity in liver mitochondria was higher in endotoxaemic mice treated with GA1N than in mice given endotoxin alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Sakaguchi
S
S
First Department of Hygienic Chemistry, Tohoku College of Pharmacy, Sendai, Japan.
Yokota
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity*; D005688:Galactosamine / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007728:Kupffer Cells / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood; D013481:Superoxides / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000378:metabolism; D014969:Xanthine Oxidase / Q000097:blood; D015054:Zymosan / Q000633:toxicity*
D004731:Endotoxins; D013481:Superoxides; D005688:Galactosamine; D015054:Zymosan; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D000410:Alanine Transaminase; D000252:Calcium-Transporting ATPases; D002118:Calcium