Phototherapy for neonatal jaundice (hyperbilirubinemia) has come into widespread use in hospitals throughout the world. Jaundiced infants are irradiated with white or light to enhance elimination of the yellow-orange neurotoxic heme catabolite, 4Z,15Z-bilirubin-IXAlpha. Yet, the molecular basis for phototherapy is not completely understood. Phototherapy causes a net increase in bilirubin elimination via formation of photoproducts that are readily excreted in bile and urine. Although accurate determination of the ratio of hepatic to renal excretion of the photoproducts is not yet determined, it seems clear that hepatic excretion is by far the major route. The key to hepatic excretion of bilirubin is its photochemical carbon-carbon double bond configurational isomerization which affords E-isomers that are more polar than the natural, more stable 4Z, 15Z isomer and sufficiently hydrophilic to cross liver into bile without resort to conjugation. Slower photochemical processes involve intramolecular cyclization and photooxidation. The former contributes in a much smaller way to hepatic excretion of bilirubin during phototherapy. The latter accounts for renally excreted photodegradation products. In an attempt to understand the primary photobiologic processes, we will try to determine why phototherapy serum of jaundiced neonates contains the 4Z, 15E (but not the 4E, 15Z) isomer of bilirubin. We pose and try to answer questions related to transport and excretion of bilirubin photoproducts. We propose to study the hepatic vs renal distribution of photoproducts and to investigate alternate pathways for bilirubin elimination.
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