Pharmacologic modification of bilirubin toxicity in tissue culture View Full Text


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Article Info

DATE

1971-08

AUTHORS

Richard P Wennberg, L Fraser Rasmussen, David Baum

ABSTRACT

While several areas of bilirubin toxicity have been identified, the mechanism of bilirubin entry into cells and the mode of cell death are not understood. Several substances which have been associated with membrane functions were examined to determine if they would influence bilirubin toxicity. Strain 929 L-cells were washed four times in protein free media and incubated one hour with the test drug before adding bilirubin. Ten μM bilirubin killed >90% cells in four hours as determined by cell penetration of erythrocin B. Hydrocortisone totally protected the cells from bilirubin toxicity; prednisolone was slightly less effective. The rate of cell death was retarded by insulin, but only in very high concentrations (0.2 units/ml). Theophylline and caffeine, which inhibit the breakdown of cyclic AMP by the enzyme phosphodiesterase, offered partial protection. Paradoxically, epinephrine and glucagon, which stimulate adenyl cyclase, and cyclic AMP and dibutyrl cyclic AMP either failed to protect or even accelerated cellular death with bilirubin. These effects could be blocked with theophylline and caffeine, suggsting that AMP or phosphodiesterase itself may be involved in bilirubin toxicity.These studies reveal additional parameters of bilirubin toxicity and suggest the possibility of altering susceptibility for kernicterus with pharmacologic agents. More... »

PAGES

420-420

Identifiers

URI

http://scigraph.springernature.com/pub.10.1203/00006450-197108000-00204

DOI

http://dx.doi.org/10.1203/00006450-197108000-00204

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1011142164


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