Long-term objectives of this proposal are to elucidate the mechanism of phototherapy for neonatal jaundice and define the structural features that control the transport and conjugation of bilirubin in the liver.
Specific aims are: (1) To measure quantum yields for photoisomerization reactions of bilirubin and its analogs and determine how these vary with wavelength and the nature of the solvent or protein environment. (2) To define, by spectroscopic and chemical methods, the structures and properties of bilirubin photoisomers and their metabolites. (3) To examine the influence of protein binding on the relative rates of excretion of bilirubin photoisomers in intact rats and the isolated rat liver. (4) To measure the wavelength dependence for photoisomerization of bilirubin in vivo in Gunn rats and humans, and evaluate the importance of skin filtration effects. (5) To quantitate plasma disappearance rates of photoisomers in humans, and develop spectroradiometric methods for predicting the therapeutic potential of phototherapy light sources. (6) To study the biliary excretion and hepatic metabolism of synthetic bilirubin model compounds in the rat. (7) To investigate the effects of acute hemolysis and administration of ethanol on the hepatic excretion of unconjugated bilirubin in rats. The project is directly related to prevention of bilirubin-induced brain damage in infants and patients with the Crigler-Najjar syndrome, to the diagnosis and understanding of liver disease, to the mechanism of gallstone formation, and to the biologic effects of sunlight and artificial visible light on humans. The results will lead to safer and more effective phototherapy methods for the treatment of neonatal jaundice and congenital unconjugated hyperbilirubinemia.
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