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. 1971 Mar;50(3):707–718. doi: 10.1172/JCI106541

Photocatabolism of labeled bilirubin in the congenitally jaundiced (Gunn) rat

J Donald Ostrow 1
PMCID: PMC291979  PMID: 5545128

Abstract

To elucidate the mechanism by which phototherapy reduces serum bilirubin, studies were performed on the catabolism of labeled bilirubin in homozygous jaundiced Gunn rats before, during, and after a period of exposure to 1700 foot candles of daylight fluorescent light. Following equilibration with the body pool of an intravenously administered tracer dose of 3H- or 14C-bilirubin, radioactive and diazo reactive compounds were excreted in the bile at a slow, steady rate and plasma specific activity declined semilogarithmically. Subsequent exposure to light caused a marked increase in the biliary excretion of radioactive and diazoreactive compounds. Fecal and urinary radioactivity increased also but remained minor fractions of the total excreted radioactivity. After extinguishing the lights, these variables reverted gradually to control values. Spectral and chromotographic analysis of the excreted pigments and their azopigments demonstrated that the increased biliary radioactivity during phototherapy consisted of two roughly equal fractions: (a) unconjugated bilirubin, excreted at rates comparable to the output of conjugated bilirubin in the bile of normal nonjaundiced rats; and (b) water-soluble bilirubin derivatives, chromatographically identical with those found in Gunn rat bile under control lighting conditions but different from the products of photodecomposition of bilirubin in vitro. In some animals, phototherapy produced little decline in plasma bilirubin despite comparable acceleration of bilirubin catabolism. This was attributed tentatively to increased synthesis of early labeled bilirubin in these animals.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARIAS I. M., JOHNSON L., WOLFSON S. Biliary excretion of injected conjugated and unconjugated bilirubin by normal and Gunn rats. Am J Physiol. 1961 May;200:1091–1094. doi: 10.1152/ajplegacy.1961.200.5.1091. [DOI] [PubMed] [Google Scholar]
  2. Bernstein R. B., Novy M. J., Piasecki G. J., Lester R., Jackson B. T. Bilirubin metabolism in the fetus. J Clin Invest. 1969 Sep;48(9):1678–1688. doi: 10.1172/JCI106133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broughton P. M., Rossiter E. J., Warren C. B., Goulis G., Lord P. S. Effect of blue light on hyperbilirubinaemia. Arch Dis Child. 1965 Dec;40(214):666–671. doi: 10.1136/adc.40.214.666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. CREMER R. J., PERRYMAN P. W., RICHARDS D. H. Influence of light on the hyperbilirubinaemia of infants. Lancet. 1958 May 24;1(7030):1094–1097. doi: 10.1016/s0140-6736(58)91849-x. [DOI] [PubMed] [Google Scholar]
  5. Callahan E. W., Jr, Schmid R. Excretion of unconjugated bilirubin in the bile of Gunn rats. Gastroenterology. 1969 Aug;57(2):134–137. [PubMed] [Google Scholar]
  6. Callahan E. W., Jr, Thaler M. M., Karon M., Bauer K., Schmid R. Phototherapy of severe unconjugated hyperbilirubinemia: formation and removal of labeled bilirubin derivatives. Pediatrics. 1970 Dec;46(6):841–848. [PubMed] [Google Scholar]
  7. DeLeon A., Gartner L. M., Arias I. M. The effect of phenobarbital on hyperbilirubinemia in glucuronyl transferase deficient rats. J Lab Clin Med. 1967 Aug;70(2):273–278. [PubMed] [Google Scholar]
  8. Diamond I., Schmid R. Neonatal hyperbilirubinemia and kernicterus. Experimental support for treatment by exposure to visible light. Arch Neurol. 1968 Jun;18(6):699–702. doi: 10.1001/archneur.1968.00470360121012. [DOI] [PubMed] [Google Scholar]
  9. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  10. FRANCOMBE W. H., TOWNSEND S. R. THE LASER IN OPHTHALMOLOGY. Can Med Assoc J. 1965 Jan 9;92:85–86. [PMC free article] [PubMed] [Google Scholar]
  11. Garay E. A., Flock E. V., Owen C. A., Jr Composition of bile pigments in the Gunn rat. Am J Physiol. 1966 Apr;210(4):684–688. doi: 10.1152/ajplegacy.1966.210.4.684. [DOI] [PubMed] [Google Scholar]
  12. Hargreaves T., Scrimgeour G. The distribution of billirubin in rat liver fractions. Experientia. 1966 Jun 15;22(6):382–383. doi: 10.1007/BF01901149. [DOI] [PubMed] [Google Scholar]
  13. Housset E., Etienne J. P., Petite J. P., Oudéa P., Oudéa M. C., Manchon P. Role du régime alimentaire sur la bilirubinémie du rat Gunn. Applications expérimentales: cholépéritoines, cholostases, action de la novobiocine. Pathol Biol. 1967 May;15(9):457–469. [PubMed] [Google Scholar]
  14. Javitt N. B. Ethereal and acyl glucuronide formation in the homozygous Gunn rat. Am J Physiol. 1966 Aug;211(2):424–428. doi: 10.1152/ajplegacy.1966.211.2.424. [DOI] [PubMed] [Google Scholar]
  15. Klaassen C. E., Roberts R. J., Plaa G. L. Maximal biliary excretion of bilirubin and sulfobromophthalein during various rates of infusion in rats of different weights and strains. Toxicol Appl Pharmacol. 1969 Jul;15(1):143–151. doi: 10.1016/0041-008x(69)90142-2. [DOI] [PubMed] [Google Scholar]
  16. LESTER R., SCHMID R. Intestinal absorption of bile pigments. II. Bilirubin absorption in man. N Engl J Med. 1963 Jul 25;269:178–182. doi: 10.1056/NEJM196307252690402. [DOI] [PubMed] [Google Scholar]
  17. Lester R., Klein P. D. Biosynthesis of tritiated bilirubin and studies of its excretion in the rat. J Lab Clin Med. 1966 Jun;67(6):1000–1012. [PubMed] [Google Scholar]
  18. NOIR B. A., GARAY E. R., ROYER M. SEPARATION AND PROPERTIES OF CONJUGATED BILIVERDIN. Biochim Biophys Acta. 1965 May 4;100:403–410. doi: 10.1016/0304-4165(65)90009-7. [DOI] [PubMed] [Google Scholar]
  19. OSTROW J. D., HAMMAKER L., SCHMID R. The preparation of crystalline bilirubin-C14. J Clin Invest. 1961 Aug;40:1442–1452. doi: 10.1172/JCI104375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ostrow J. D., Branham R. V. Photodecomposition of bilirubin and biliverdin in vitro. Gastroenterology. 1970 Jan;58(1):15–25. [PubMed] [Google Scholar]
  21. Ostrow J. D., Murphy N. H. Isolation and properties of conjugated bilirubin from bile. Biochem J. 1970 Nov;120(2):311–327. doi: 10.1042/bj1200311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Roberts R. J., Klaassen C. D., Plaa G. L. Maximum biliary excretion of bilirubin and sulfobromophthalein during anesthesia-induced alteration of rectal temperature. Proc Soc Exp Biol Med. 1967 May;125(1):313–316. doi: 10.3181/00379727-125-32080. [DOI] [PubMed] [Google Scholar]
  23. Roberts R. J., Plaa G. L. Effect of phenobarbital on the excretion of an exogenous bilirubin load. Biochem Pharmacol. 1967 May;16(5):827–835. doi: 10.1016/0006-2952(67)90055-x. [DOI] [PubMed] [Google Scholar]
  24. Robinson S. H. Increased bilirubin conjugation in heterozygous Gunn rats treated with phenobarbital. Nature. 1969 Jun 7;222(5197):990–991. doi: 10.1038/222990a0. [DOI] [PubMed] [Google Scholar]
  25. Robinson S. H., Lester R., Crigler J. F., Jr, Tsong M. Early-labeled peak of bile pigment in man. Studies with glycine-14C and delta-aminolevulinic acid-3H. N Engl J Med. 1967 Dec 21;277(25):1323–1329. doi: 10.1056/NEJM196712212772501. [DOI] [PubMed] [Google Scholar]
  26. Robinson S. H. The origins of bilirubin. N Engl J Med. 1968 Jul 18;279(3):143–149. doi: 10.1056/NEJM196807182790306. [DOI] [PubMed] [Google Scholar]
  27. SCHMID R., HAMMAKER L. METABOLISM AND DISPOSITION OF C14-BILIRUBIN IN CONGENITAL NONHEMOLYTIC JAUNDICE. J Clin Invest. 1963 Nov;42:1720–1734. doi: 10.1172/JCI104858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schmid R., Diamond I., Hammaker L., Gundersen C. B. Interaction of bilirubin with albumin. Nature. 1965 Jun 5;206(988):1041–1043. doi: 10.1038/2061041b0. [DOI] [PubMed] [Google Scholar]
  29. Schmid R., Marver H. S., Hammaker L. Enhanced formation of rapidly labelled bilirubin by phenobarbital: hepatic microsomal cytochromes as a possible source. Biochem Biophys Res Commun. 1966 Aug 12;24(3):319–328. doi: 10.1016/0006-291x(66)90158-6. [DOI] [PubMed] [Google Scholar]
  30. Trolle D. Decrease of total serum-bilirubin concentration in newborn infants after phenobarbitone treatment. Lancet. 1968 Sep 28;2(7570):705–708. doi: 10.1016/s0140-6736(68)90750-2. [DOI] [PubMed] [Google Scholar]
  31. Van Roy F. P., Heirwegh K. P. Determination of bilirubin glucuronide and assay of glucuronyltransferase with bilirubin as acceptor. Biochem J. 1968 Apr;107(4):507–518. doi: 10.1042/bj1070507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. WEBER A. P., SCHALM L. Quantitative separation and determination of bilirubin and conjugated bilirubin in human serum. Clin Chim Acta. 1962 Nov;7:805–810. doi: 10.1016/0009-8981(62)90063-3. [DOI] [PubMed] [Google Scholar]
  33. Yaffe S. J., Levy G., Matsuzawa T., Baliah T. Enhancement of glucuronide-conjugating capacity in a hyperbilirubinemic infant due to apparent enzyme induction by phenobarbital. N Engl J Med. 1966 Dec 29;275(26):1461–1466. doi: 10.1056/NEJM196612292752602. [DOI] [PubMed] [Google Scholar]
  34. ZILVERSMIT D. B. The design and analysis of isotope experiments. Am J Med. 1960 Nov;29:832–848. doi: 10.1016/0002-9343(60)90117-0. [DOI] [PubMed] [Google Scholar]

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