Factors influencing toxicity of bilirubin in cerebellum tissue culture

Abstract

We have studied the relationship of pH and bilirubin:albumin ratio to the occurrence of bilirubin-induced damage in cerebellum cultures. Sufficient unbound bilirubin reproducibly caused a sequence of histologic changes which were observed by light microscopy. At a constant bilirubin:albumin molar ratio, a decrease in pH of the medium resulted in proportionately greater cytotoxicity. Maintenance of an average medium pH above 7.62 during the last 12 hours of the cultures' lives prevented damage in the presence of bilirubin concentrations of up to 50 mg. per 100 ml. At lower pH values an increase in the bilirubin:albumin ratio produced increasingly greater cytotoxicity. These findings support the thesis that unbound, unconjugated bilirubin is responsible for neurologic damage. Knowledge of several conditions, i.e., pH, bilirubin:albumin molar ratio, and duration of exposure, is necessary to predict the occurrence of damage. The regional pattern of bilirubin crystallization suggests that regional pH differences may play a part in determining in vivo distribution of lesions in kernicterus.