Mechanisms of bilirubin toxicity.
Possible mechanisms of bilirubin toxicity on the brain and lung were studied in animal experiments and in vitro. The uptake of tyrosine as precursor of dopamine in rat synaptosomes was evaluated to study the role of different bilirubin concentrations on synaptic neurotransmission. The results of this study show a statistically significant correlation between bilirubin levels and tyrosine uptake, supporting the hypothesis that the effect of bilirubin on neuronal excitability is dose-dependent. Concerning bilirubin toxicity on the lung, we studied the effect of different bilirubin concentrations on surface activity of modified natural surfactant (Curosurf) and synthetic surfactant (Exosurf), both in current clinical use for treatment of neonatal respiratory distress syndrome. Surface activity of Curosurf and Exosurf was investigated with the captive bubble surfactometer. The results of this study show that bilirubin impairs, in vitro, the surface tension activity of natural surfactant in a dose dependent manner and has no effect on surface tension activity of artificial surfactant. These data suggest that bilirubin interferes with surfactant proteins SP-B and/or SP-C, thus impairing surfactant activity at the air-liquid interface. We conclude that bilirubin shows its toxic effect reacting with different biological systems in a dose-dependent fashion.
Department of Paediatrics, Bruderholz Hospital, Basel (BL), Switzerland.
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D000818:Animals; D001663:Bilirubin / Q000633:toxicity*; D001688:Biological Products; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005233:Fatty Alcohols; D006932:Hyperbilirubinemia / Q000503:physiopathology; D008297:Male; D010743:Phospholipids; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; D011663:Pulmonary Surfactants; D051381:Rats; D017207:Rats, Sprague-Dawley; D013500:Surface Tension; D014443:Tyrosine / Q000378:metabolism
D001688:Biological Products; D004338:Drug Combinations; D005233:Fatty Alcohols; D010743:Phospholipids; D011663:Pulmonary Surfactants; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; D014443:Tyrosine; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; C068291:poractant alfa; D001663:Bilirubin