Additive effect of tumor necrosis factor-alpha and endotoxin on bilirubin cytotoxicity.
Clinical observations suggest that sepsis may enhance the risk of kernicterus. This study investigated the combined effects of bilirubin, endotoxin, and tumor necrosis factor-alpha (TNF-alpha), which simulate sepsis in a jaundiced mouse fibroblast cell line. The horseradish peroxidase oxidation method was applied for bilirubin-albumin titration studies to test the effect of endotoxin and TNF-alpha on bilirubin-albumin binding. A modified 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide method was used to study cytotoxicity. Bilirubin caused cytotoxicity in a dose-dependent manner in the cultured mouse fibroblasts. Such an effect was significantly amplified by TNF-alpha and endotoxin. TNF-alpha and endotoxin had no effect on the bilirubin-albumin titration curves. Our results have shown that TNF-alpha and endotoxin increase the cytotoxicity of bilirubin. These findings provide supportive evidence that sepsis would increase the risk of tissue damage by bilirubin.
Ngai
K C
KC
Department of Paediatrics, University of Hong Kong, Queen Mary Hospital, China.
Yeung
C Y
CY
D000704:Analysis of Variance; D000818:Animals; D001663:Bilirubin / Q000378:metabolism / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004347:Drug Interactions; D004730:Endothelium, Vascular; D004731:Endotoxins / Q000633:toxicity*; D005909:Glioblastoma; D006801:Humans; D007700:Kinetics; D007739:L Cells; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver; D051379:Mice; D009447:Neuroblastoma; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D014471:Umbilical Veins
D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D001663:Bilirubin