Abstract
ABSTRACT: The toxicity of bilirubin was investigated in 2 neural cell lines NBR10A and N115 using a quantitative dye assay 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium biomide (MTT) as a measure of cell viability and [3H]thymidine incorporation as a measure of DNA synthesis. Short exposures (up to 2 h) to bilirubin, even up to a bilirubin-albumin molar ratio of 1.5, yielded no evidence of toxicity using these assays. At longer exposure times (24 h) a decrease in cell viability and [3H]thymidine incorporation was detected at a molar ratio of 0.8 when the bilirubin concentration was 0.1 mM or higher, whereas lower bilirubin levels at this molar ratio showed no deleterous effect. The effect of bilirubin is more pronounced at a molar ratio of 1.5 with longer incubation periods. The MTT assay showed the N115 cells appeared to be more resistant to bilirubin cytotoxicity than NBR10A cells, a finding which was not obtained from [3H]thymidine incorporation studies. This discrepancy can be explained by the fact that we are measuring two different variables; the MTT assay estimates the number of viable cells at the end of the experiment by measuring mitochondrial function whereas the [3H]thymidine assay measures the rate of DNA synthesis during the last 2 h of the experiment. The concentration effect of bilirubin is evident from the [3H]- thymidine studies in that at a molar ratio of 1.5 and bilirubin concentration of 0.075 mM or higher, there is both cell kill (decrease in DNA) and inhibition of [3H]- thymidine incorporation (decrease in specific activity). When the bilirubin concentration is reduced to 0.03 mM, there is little or no cell death (no change DNA) but inhibition still exists (42% decrease in specific activity). Thus, cell viability and function of these two neural lines is dependent not only on the bilirubin albumin molar ratio, but also on the absolute concentration of bilirubin and albumin as well as the time of exposure.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schiff, D., Chan, G. & Poznansky, M. Bilirubin Toxicity in Neural Cell Lines N115 and NBR10A. Pediatr Res 19, 908–911 (1985). https://doi.org/10.1203/00006450-198509000-00007
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1203/00006450-198509000-00007
This article is cited by
-
Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats
Journal of Nanoparticle Research (2015)
-
Bilirubin and Amyloid-β Peptide Induce Cytochrome c Release Through Mitochondrial Membrane Permeabilization
Molecular Medicine (2000)
-
Renal function in obstructive jaundice in man: Cholangiocarcinoma model
Kidney International (1990)