Gadolinium chloride prevents mortality in hepatectomized rats given endotoxin.
The purpose of this study was to determine if inhibition of Kupffer cells by gadolinium chloride (GdCl(3)) affects the arterial ketone body ratio (AKBR), liver injury, and mortality in hepatectomized rats administered lipopolysaccharide (LPS). Rats treated with or without GdCl(3) received a 70% hepatectomy. Either LPS (5 mg/kg) or vehicle (saline) was administered 48 h after hepatectomy. Further, hepatectomized rats were administered superoxide dismutase (CuZnSOD, 9 x 10(4) U/kg) before and every 3 h after LPS injection up to 9 h to assess involvement of superoxide in liver injury in this model. All hepatectomized rats with saline died within 24 h after LPS administration. In contrast, GdCl(3) prevented this mortality completely. Serum AST levels were about 160 IU/L in hepatectomized rats with vehicle; however, values were increased approximately 25-fold by LPS administration. In contrast, these increases were blunted significantly by about 90% by GdCl(3). Further, GdCl(3) also prevented decreases in AKBR caused by LPS. LPS caused severe liver injury, which was stopped almost completely by GdCl(3). LPS-induced increases in superoxide production by isolated Kupffer cells were stopped by about 90% by GdCl(3). Importantly, SOD administration prevented decreases in AKBR, liver injury, and mortality significantly as well as GdCl(3). These results indicated that GdCl(3) prevented liver injury and mortality caused by LPS most likely by inhibiting superoxide production by Kupffer cells. Thus, inhibition of activation of Kupffer cells could be useful for preventing liver dysfunction in postoperative endotoxemia.
First Department of Surgery, Yamanashi Medical University, Yamanashi, Japan. hkouno@res.yamanashi-med.ac.jp
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Kono
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Fujii
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Matsuda
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Yamamoto
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Matsumoto
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001158:Arteries; D001663:Bilirubin / Q000097:blood; D004731:Endotoxins / Q000494:pharmacology*; D005682:Gadolinium / Q000494:pharmacology*; D006498:Hepatectomy; D007657:Ketone Bodies / Q000097:blood; D007728:Kupffer Cells / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D010976:Platelet Count; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004731:Endotoxins; D007657:Ketone Bodies; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D005682:Gadolinium; D000410:Alanine Transaminase; C038958:gadolinium chloride; D001663:Bilirubin