Quinine inhibits release of tumor necrosis factor, apoptosis, necrosis and mortality in a murine model of septic liver failure.
We investigated the effect of quinine on liver injury induced by lipopolysaccharide in mice sensitized with D-galactosamine. This model is characterized by high systemic release of tumor necrosis factor, which mediates hepatic apoptosis and necrosis. Pretreatment with quinine, a K+ channel blocker, prevented formation of tumor necrosis factor (TNF) as well as the subsequent hepatic DNA fragmentation and liver enzyme leakage. Thus, inhibition of K+ channels may be a novel therapeutic approach in cytokine-related organ damage.
Gantner
F
F
Department of Biochemical Pharmacology, University of Konstanz, Germany.
Uhlig
S
S
Wendel
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D005688:Galactosamine / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D017093:Liver Failure / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011803:Quinine / Q000627:therapeutic use*; D051381:Rats; D012475:Salmonella / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D015221:Potassium Channels; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D004247:DNA; D011803:Quinine