In Vitro and In Vivo Bilirubin-Sensitized Photoeffects at the Molecular and Cellular Levels

  • John D. Spikes


Phototherapy as a treatment for neonatal hyperbilirubinemia has now been in use for approximately twenty-five years. Its effectiveness in reducing the serum bilirubin levels in the newborn, especially in premature infants, is well recognized. Acute complications arising from the use of phototherapy have been rare and none are apparently considered to be serious. Further, at present, there does not appear to be much evidence for the development of long term complications in those individuals who have received phototherapy.12 However, it should be kept in mind that bilirubin is a photodynamic sensitizer — a phototoxic agent — which, although rather inefficient compared to many sensitizers,3 demonstrably sensitizes photodamage at the molecular and cellular levels, both in vitro and in vivo. Thus patients should be observed carefully during phototherapeutic treatment and should receive only the minimum necessary light dose. In this review I will briefly summarize a few aspects of bilirubin photochemistry pertinent to photosensitized eactions and then examine the known photosensitizing effects of bilirubin in biological systems.


Human Serum Albumin Singlet Oxygen Serum Bilirubin Level Furfuryl Alcohol Osmotic Fragility 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    A.K. Brown and A.F. McDonagh, Phototherapy for neonatal hyperbilirubinemia: Efficacy, mechanism and toxicity, Adv. Pediatr 27:341 (1980).Google Scholar
  2. 2.
    A.N. Cohen and J.D. Ostrow, New concepts in phototherapy: Photoisomerization of bilirubin IX-alpha and potential toxic effects of light, Pediatr 65: 740 (1980).Google Scholar
  3. 3.
    J.D. Spikes, Photodynamic reactions in photomedicine, p. 113 in: The Science of Photomedicine, J.D. Regan and J.A. Parrish, eds., Plenum publishing Corp., New York (1982).Google Scholar
  4. 4.
    A.F. McDonagh, Bile pigments: bilatrienes and 5,15: biladienes, p. 293, in: “The Porphyrins,” Vol. VIA, D. Dolphin, ed., Academic Press, New York (1979).Google Scholar
  5. 5.
    D.A. Lightner, Structure, photochemistry and organic chemistry of bilirubin, p. 1, in: Bilirubin, Vol. 1, K.P.M. Heirwegh and S.B. Brown, eds., CRC Press, Boca Raton, (1982).Google Scholar
  6. 6.
    A.E. Myshkin and V.N. Sakharov, The photochemistry of bilirubin, Russ. Chem. Rev 51:40 (1982). Transl. from Uspekhi Khimii 51:72 (1982).Google Scholar
  7. 7.
    E.J. Land, The triplet excited state of bilirubin, Photochem. Photobiol 24:475 (1976).Google Scholar
  8. 8.
    R.W. Sloper and T.G. Truscott, The quantum yield for bilirubin photoisomerization, Photochem. Photobiol 35:743 (1982).Google Scholar
  9. 9.
    A.F. McDonagh, L.A. Palma and D.A. Lightner, Blue light and bilirubin excretion, Science 208: 145 (1980).Google Scholar
  10. 10.
    A.A. Lamola, J. Flores and F.H. Doleiden, Quantum yield and equilibrium position of the configurational photoisomerization of bilirubin bound to human serum albumin, Photochem. Photobiol 35:649 (1982).Google Scholar
  11. 11.
    P. Manitto, D. Monti, and E. Garbagnati, Photochemical addition of N-acetyl-L-cysteine and glutathione to bilirubin in vitro and its relevance to phototherapy of jaundice, Farmaco Ed. Sci 27:999 (1972).Google Scholar
  12. 12.
    G. Jori, F. Rubaltelli and E. Rossi, Photoinduced modification of human serum albumin during phototherapy of jaundiced newborns, Springer Ser. Opt. Sci 22:145 (1980).Google Scholar
  13. 13.
    G. Jori, E. Rossi, and F. F. Rubaltelli, Phototherapy-induced covalent binding of bilirubin to serum albumin, Pediatr Res. 14: 1363 (1980).Google Scholar
  14. 14.
    F.F. Rubaltelli and G. Jori, Visible light irradiation of human and bovine serum albumin-bilirubin complex, Photochem. Photobiol 29:991 (1979).Google Scholar
  15. 15.
    D.F. Davidson, I.R. Hainsworth, R. Rowan, G. Kousourou and M. Colgan, Possible effect of bilirubin concentration on the in-vitro lability of creatine kinase during storage, Ann. Clin. Biochem 18:185 (1981).Google Scholar
  16. 16.
    M.R. Deziel and A.W. Girotti, Photodynamic action of bilirubin on liposomes and erythrocyte membranes, J Biol. Chem 255:8192 (1980).Google Scholar
  17. 17.
    W.T. Speck and H.S. Rosenkranz, The bilirubin-induced photo-degradation of deoxyribonucleic acid, Pediatr. Res 9:703 (1975).Google Scholar
  18. 18.
    A.F. McDonagh and L.A. Palma, Mechanism of bilirubin photodegradation: role of singlet oxygen, p. 81 in “Fogarty International Proceedings No. 35”, P.D. Berk and N.I. Berlin, eds., U.S. Gov’t. Printing Office, Washington, D.C. (1976).Google Scholar
  19. 19.
    W. Hausmann, Ueber die sensibilisierende Wirkung tierischer Farbstoffe und ihre physiologische Bedeutung, Biochem. Z 14:275 (1908).Google Scholar
  20. 20.
    K. Saeki, Studies in the photodynamic hemolytic action of bilirubin. I, II, III, IV, Jap. J. Gastroenterol 4:153, 166, 231, 244 (1932). Chem. Abstr. 27: 1018, 1041 (1933).Google Scholar
  21. 21.
    G.B. Odell, R.S. Brown, and A.E. Kopelman, The photodynamic action of bilirubin on erythrocytes, J Pediatr 81: 473 (1972).Google Scholar
  22. 22.
    M.G. Blackburn, M.M. Orzalesi, and P. Pigram, Effect of light and bilirubin on fetal red blood cells in vitro, Biol. Neonate 21:35 (1974).Google Scholar
  23. 23.
    E.M. Ostrea and G.B. Odell, Photosensitized shift in the 02 dissociation curve of fetal blood, Acta Paediatr. Scand 63:341 (1974).Google Scholar
  24. 24.
    M. Castro, S.G. Tambucci, A. Panero, O. Giardini, and M. Orzalesi, Studio in vitro degli effetti della luce sui lipidi del globula rosso, Min. Pediat 28:391 (1976).Google Scholar
  25. 25.
    A.W. Girotti, Photodynamic action of bilirubin on human erythrocyte membranes. Modification of polypeptide constituents, Biochemistry 14: 3377 (1975).Google Scholar
  26. 26.
    A.W. Girotti, Bilirubin-photosensitized cross-linking of polypeptides in the isolated membrane of the human erythrocyte, J. Biol. Chem 253:7186 (1978).Google Scholar
  27. 27.
    A.W. Girotti, Bilirubin-sensitized photoinactivation of enzymes in the isolated membrane of the human erythrocyte, Photochem. Photobiol 24:525 (1976).Google Scholar
  28. 28.
    M.R. Deziel and A.W. Girotti, Bilirubin-photosensitized lysis of resealed erythrocyte membranes, Photochem. Photobiol 31:593 (1980).Google Scholar
  29. 29.
    M. R. Deziel and A.W. Girotti, Lysis of research erythrocyte ghosts by photoactivated tetrapyrroles: Estimation of photolesion dimension, Int. J. Biochem 14:263 (1982).Google Scholar
  30. 30.
    T. Taura and T. Murata, Effect of bilirubin photo-oxidation on frog crystalline lens fiber membrane, Nippon Ganka Gakkai Zasshi 83: 77 (1980).Google Scholar
  31. 31.
    D.D. Hackney, Photodynamic action of bilirubin on the inner mitochondrial membrane. Implications for the organization of the mitochondrial ATPase, Biochem. Biophys. Res. Commun 94:875 (1980).Google Scholar
  32. 32.
    M.D. Maines and A. Kappas, The degradative effects of porphyrins and heme compounds on components of the microsomal mixed function oxidase system. J. Biol. Chem 250:2363 (1975).Google Scholar
  33. 33.
    A.D. Rahimtula, F. J. Hawco and P.J. O’Brien, The involvement of 102 in the inactivation of mixed function oxidase and peroxidation of membrane lipids during the photosensitized oxidation of liver microsomes, Photochem. Photobiol 28:811 (1978).Google Scholar
  34. 34.
    F. Meyer-Betz, Untersuchungen ueber die biologische (photodynamische) Wirkung des Haematoporphyrins und anderer Derivate des Blut-und Gallenfarbstoffs, Deutsch. Arch. Klin. Med 112:476 (1913).Google Scholar
  35. 35.
    S.H. Robinson and A. Schunior, Hemolytic anemia induced by light therapy in jaundiced rats, Soc. Exptl. Biol. Med 158:81 (1978).Google Scholar
  36. 36.
    J.O. Cukier, A.C. Maglalang, and G.B. Odell, Increased osmotic fragility of erythrocytes in chronically jaundiced rats after phototherapy, Acta Paediatr. Scand 68:903 (1979).Google Scholar
  37. 37.
    R.B. Howe, C.R. Hadland and R.R. Engel, Effect of phototherapy on serum bilirubin levels and red blood cell survival in congenitally jaundiced Gunn rats, J. Lab. Clin. Med 92:221 (1978).Google Scholar
  38. 38.
    F.F. Rubalteili, G. Jori and E. Rossi, Evidence of minor damage occurring during phototherapy: Photoinduced covalent binding of bilirubin to serum albumin, p. 79, in: “Intensive Care of the Newborn,” Vol. III, L. Stern, F.-H. Bent and K. Paul, eds., Waverly Press, Baltimore (1981).Google Scholar
  39. 39.
    E. John, Complications of phototherapy in hyperbilirubinemia, Aust. Paediat. J 11:53 (1975).Google Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • John D. Spikes
    • 1
  1. 1.Department of BiologyUniversity of UtahSalt Lake CityUSA

Personalised recommendations