Molecular Mechanisms of Phototherapy of Neonatal Jaundice

  • Antony F. McDonagh
Chapter

Abstract

The success of phototherapy depends on photochemical transformations of bilirubin within light-exposed tissues. These reactions alter the structure of bilirubin in such a way that the intact molecule or fragments of it can be excreted via the kidney or liver without having to undergo further metabolic modification. So far three photochemical reactions of bilirubin have been shown to occur in vivo, and it is likely that these three together account for most of the effect of light on bilirubin metabolism in jaundiced newborns. The three reactions are photooxidation, configurational isomerization, and structural isomerization. In this presentation I shall discuss briefly some of our evidence for the occurrence of these reactions in vivo and speculate on their relative contributions to the net effect of phototherapy. Since the interpretation of the in vivo studies is very much dependent on knowledge gleaned from in vitro photochemical studies, I shall begin with a discussion of the latter.

Keywords

Human Serum Albumin Dimethyl Ester Neonatal Jaundice COOH COOH Bile Fistula 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    D.A. Lightner, Structure, photochemistry, and organic chemistry of bilirubin, in: “Bilirubin”, K.P.M. Heirwegh and S.B. Brown, eds., CRC Press, Boca Raton (1982).Google Scholar
  2. 2.
    D.A. Lightner, W.P. Linnane, and C.E. Ahlfors, Bilirubin photooxidation products in the urine of phototherapy neonates, Submitted for publication.Google Scholar
  3. 3.
    A.F. McDonagh, D.A. Lightner, and T.A. Wooldridge, Geometric isomerization of bilirubin-IXa and its dimethyl ester. J. Chem. Soc. Chem. Commun. 110 (1979).Google Scholar
  4. 4.
    R. Bonnett, J.E. Davis, M.B. Hursthouse, and G.M. Sheldrick, The structure of bilirubin, Proc. Roy. Soc. Lond. B. 202: 249 (1978).Google Scholar
  5. 5.
    A.F. McDonagh, L.A. Palma, F.R. Trull, and D.A. Lightner, Phototherapy for neonatal jaundice. Configurational isomers of bilirubin, J. Am. Chem. Soc. 102: 6865 (1982).Google Scholar
  6. 6.
    H. Falk, N. Muller, M. Ratzenhofer, and K. Winsauer, The structure of “Photobilirubin”, Monatsh. Chem. 113:1421 (1982).Google Scholar
  7. 7.
    J.F. Ennever, A.F. McDonagh, and W.T. Speck, Phototherapy for neonatal jaundice: Optimal wavelengths of light, J. Pediatr. In press.Google Scholar
  8. 8.
    J.A. de Groot, R. van der Steen, R. Fokkens, and J. Lugtenburg, Synthesis and photoisomerisation of 2,3,17,18,22-pentamethyl-10,23-dihydro-1,19-[21H,24H]-bilindione, an unsymmetrical bilirubin model compound, Recl. Tray. Chim. Pays-Bas 101:219 (1982).Google Scholar
  9. 9.
    J.A. de Groot, R. van der Steen, R. Fokkens, and J. Lugtenburg, Synthesis and photochemical reactivity of bilirubin model compounds, Recl. Tray. Chim. Pays-Bas 101:35 (1982).Google Scholar
  10. 10.
    A.F. McDonagh, L.A. Palma, and D.A. Lightner, Phototherapy for neonatal jaundice. Stereospecific and regioselective photoisomerization of bilirubin bound to human serum albumin and NMR characterization of intramolecularly cyclized photoproducts, J. Am. Chem. Soc. 104:6867 (1982).Google Scholar
  11. 11.
    B.I. Green, A.A. Lamola, and C.V. Shank, Picosecond primary photoprocesses of bilirubin bound to human serum albumin, Proc. Natl. Acad. Sci. USA 78:2008 (1981).Google Scholar
  12. 12.
    M.S. Stoll, N. Vicker, C.H. Gray, and R. Bonnett, Concerning the structure of photobilirubin II, Biochem. J. 201:179 (1982).Google Scholar
  13. 13.
    M.S. Stoll, E.A. Zenone, J.D. Ostrow, and J.E. Zarembo, Preparation and properties of bilirubin photoisomers, Biochem. J. 183:139 (1979).Google Scholar
  14. 14.
    S. Onishi, K. Isobe, S. Itoh, N. Kawade, and S. Sugiyama, Demonstration of a geometric isomer of bilirubin-IX in the serum of a hyperbilirubinaemic newborn infant and the mechanism of jaundice phototherapy, Biochem. J. 190:533 (1980).Google Scholar
  15. 15.
    A.F. McDonagh, Bile Pigments: Bilatrienes and 5,15-biladienes, in: “The Porphyrins”, D. Dolphin, ed., Academic Press, New York (1979).Google Scholar
  16. 16.
    S. Onishi, S. Itoh, N. Kawade, K. Isobe, and S. Sugiyama, The separation of configurational isomers of bilirubin by high pressure liquid chromatography and the mechanism of jaundice phototherapy, Biochem. Biophys. Res. Commun. 90:890 (1979).Google Scholar
  17. 17.
    A.F. McDonagh, and L.M. Ramonas, Jaundice phototherapy: Micro flow-cell photometry reveals rapid biliary response of Gunn rats to light, Science 201: 829 (1978).Google Scholar
  18. 18.
    C.S. Berry, J.E. Zarembo, and J.D. Ostrow, Evidence for conversion of bilirubin to dihydroxyl derivatives in the Gunn rat, Biochem. Biophys. Res. Commun. 49:1366 (1972).Google Scholar
  19. 19.
    A.F. McDonagh, L.A. Palma, and D.A. Lightner, Blue light and bilirubin excretion, Science 208: 145 (1980).Google Scholar
  20. 20.
    A.F. McDonagh, unpublished observations.Google Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Antony F. McDonagh
    • 1
  1. 1.The Liver Center and Department of MedicineUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations