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8402 human cell culture — A model for evaluating bilirubin-albumin interactions with drug
Authors:Arun K. Pramanik  Nancy Horn  Gregory Schwemer
Affiliation:1. Department of Pediatrics, Health Sciences Center, Tucson, AZ, U.S.A.;2. LSU School of Medicine, Shreveport, LA U.S.A.
Abstract:The effect of therapeutic concentration of sulfisuxazole (sulfa) on the bilirubin uptake and viability of 8402 cells in culture was studied. The total bilirubin was kept constant at 24 μM and albumin was added to obtain bilirubin-albumin molar ration (BAMR) ranging from 0.5 to 2. The effect of sulfa on unbound bilirubin (UB) was measured by the peroxidase assay. Sulfa increased UB at all BAMR's more so at 1.5 and 2.0 (P < 0.05). Significant increase in bilirubin uptake/cell with a corresponding decrease in cell viability was noted with sulfa at BAMR's > 1 (P < 0.05). The LD50 of these cells was 73–86 nM of UB. A plot of cell viability versus UB for the combined control and sulfa data (r2 = 0.94) confirms that the decrease in cell viability with increasing BAMR is explained by the corresponding rise in UB. Therefore, increase in UB by sulfa leads to toxicity of 8402 cells. Thus, we speculate that they may be used to study the mechanism of bilirubin neurotoxicity induced by similar drugs.
Keywords:Address all reprint requests and correspondence to: Arun K. Pramanik   M.D.   Department of Pediatrics   LSU School of Medicine   P.O. Box 33932   Shreveport   LA 71130   U.S.A.
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