Tumor necrosis factor alpha alters the cytotoxic effect of hydrogen peroxide in cultured hepatocytes.
We examined whether tumor necrosis factor-alpha (TNF) affects the cytotoxic capacity of reactive oxygen species on rat hepatocytes in culture. Both TNF and reactive oxygen species are involved in many inflammatory events including hepatic ischemia/reperfusion injury and endotoxic shock. Synchronous treatment of hepatocytes with both TNF and H2O2 demonstrated that TNF (2000 ng/ml) enhanced the cytotoxic effect of H2O2 (500 microM). By contrast, pretreatment with TNF (2000 ng/ml) for 24 h followed by exposure to H2O2 (1000 microM) reduced the reactive oxygen-induced cytotoxicity. We conclude that TNF increases the effects of reactive oxygen-induced cytotoxicity when exposed synchronously, whereas TNF pretreatment induces a cytoprotective effect to reactive oxygen species, presumably by up-regulation of the reduced form of glutathione levels in hepatocytes.
Imanishi
H
H
Department of Surgery, The University of Michigan Medical School, Ann Arbor 48109, USA.
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D000704:Analysis of Variance; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D002374:Catalase; D005978:Glutathione; D019803:Glutathione Disulfide