8402 human cell culture--a model for evaluating bilirubin-albumin interactions with drug

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 microM and albumin was added to obtain bilirubin-albumin molar ratio (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 less than 0.05). Significant increase in bilirubin uptake/cell with a corresponding decrease in cell viability was noted with sulfa at BAMR's greater than 1 (P less than 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.