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Vol. 89, No. 3, 2006
Issue release date: April 2006
Section title: Original Paper
Biol Neonate 2006;89:139–146
(DOI:10.1159/000088717)

The Effectiveness of Oral Tin Mesoporphyrin Prophylaxis in Reducing Bilirubin Production after an Oral Heme Load in a Transgenic Mouse Model

DeSandre G.H. · Wong R.J. · Morioka I. · Contag C.H. · Stevenson D.K.
Department of Pediatrics, Stanford University School of Medicine, Stanford, Calif., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 5/30/2005
Accepted: 8/12/2005
Published online: 4/6/2006

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 0

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO

Abstract

Background: Neonatal jaundice is commonly encountered and rarely associated with morbidity and mortality. Nonetheless, infants with glucose-6-phosphate dehydrogenase deficiency often have hemolysis (a heme load) caused by an environmental oxidant trigger, thus increasing their risk for serious morbidity. The use of tin mesoporphyrin (SnMP) has been proposed for interdicting the development of severe hyperbilirubinemia in a variety of conditions. Objectives: We studied the in vivo effects of prophylactic oral SnMP on heme oxygenase (HO) activity and bilirubin production, as indexed by the excretion rate of carbon monoxide (VeCO), following a subsequent oral heme load. Methods: Adult mice were exposed serially to heme and assessed for in vivo bilirubin production rates, HO-1 transcription and protein, and HO activity. The effect of prophylaxis with a single oral dose of SnMP prior to an oral heme load was assessed by measuring VeCOand tissue HO activities. Results: After serial heme exposures, VeCO, HO-1 transcription and protein, and liver and spleen HO activities increased incrementally. After pretreatment with oral SnMP, bilirubin production decreased in response to an oral heme load. Also, heme-mediated increases in liver, spleen, and intestine HO activities were significantly dampened. Conclusions: A single oral dose of SnMP results in durable inhibition of bilirubin production and HO activity for at least 24 h in a mouse model of oral heme loading. Further studies are needed to fully elucidate the duration of this protection against hyperbilirubinemia due to a delayed heme load and any long-term consequences of prophylaxis with SnMP on HO-1 transcription and HO-1 protein.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 5/30/2005
Accepted: 8/12/2005
Published online: 4/6/2006

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 0

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Landaw SA, Winchell HS, Boone RF: Measurement of endogenous carbon monoxide production in hemolytic disease of the inborn. Clin Res 1971;19:208A.
  2. Coburn RF, Wallace HW, Abboud R: Redistribution of body carbon monoxide after hemorrhage. Am J Physiol 1971;220:868–873.
  3. Valaes T, Drummond GS, Kappas A: Control of hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient newborns using an inhibitor of bilirubin production, Sn-mesoporphyrin. Pediatrics 1998;101:E1–E7.
  4. Hayde M, Widness JA, Pollak A, Kohlhauser-Vollmuth C, Vreman HJ, Stevenson DK: Rhesus isoimmunization: increased hemolysis during early infancy. Pediatr Res 1997;41:716–721.
  5. Kaplan M, Muraca M, Hammerman C, Vilei MT, Leiter C, Rudensky B, Rubaltelli FF: Bilirubin conjugation, reflected by conjugated bilirubin fractions, in glucose-6-phosphate dehydrogenase-deficient neonates: a determining factor in the pathogenesis of hyperbilirubinemia. Pediatrics 1998;102:E37–E42.

    External Resources

  6. Stevenson DK, Wong RJ, DeSandre GH, Vreman HJ: A primer on neonatal jaundice. Adv Pediatr 2004;51:263–288.

    External Resources

  7. Maines MD: Heme oxygenase: Clinical Applications and Functions. Boca Raton, FL, CRC Press, 1992, pp 203–206.
  8. Rodgers PA, Stevenson DK: Developmental biology of heme oxygenase. Clin Perinatol 1990;17:275–291.
  9. Lincoln BC, Healey JF, Bonkovsky HL: Regulation of hepatic haem metabolism. Disparate mechanisms of induction of haem oxygenase by drugs and metals. Biochem J 1988;250:189–196.
  10. Shibahara S, Muller RM, Taguchi H: Transcriptional control of rat heme oxygenase by heat shock. J Biol Chem 1987;262:12889–12892.
  11. Maines MD: Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 1988;2:2557–2568.
  12. Choi AM, Alam J: Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am J Respir Cell Mol Biol 1996;15:9–19.
  13. Vreman HJ, Stevenson DK: Heme oxygenase activity as measured by carbon monoxide production. Anal Biochem 1988;168:31–38.
  14. Ip S, Chung M, Kulig J, O’Brien R, Sege R, Glicken S, Maisels MJ, Lau J: An evidence-based review of important issues concerning neonatal hyperbilirubinemia. Pediatrics 2004;114:E130–E153.

    External Resources

  15. Kaplan M, Hammerman C: Understanding and preventing severe neonatal hyperbilirubinemia: is bilirubin neurotoxicity really a concern in the developed world? (review) Clin Perinatol 2004;31:555–575.
  16. American Academy of Pediatrics: Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297–316.
  17. Kaplan M, Hammerman C, Maisels MJ: Bilirubin genetics for the nongeneticist: hereditary defects of neonatal bilirubin conjugation. Pediatrics 2003;111:886–893.
  18. Vreman HJ, Cipkala DA, Stevenson DK: Characterization of porphyrin heme oxygenase inhibitors. Can J Physiol Pharmacol 1996;74:278–285.
  19. Vreman HJ, Ekstrand BC, Stevenson DK: Selection of metalloporphyrin heme oxygenase inhibitors based on potency and photoreactivity. Pediatr Res 1993;33:195–200.
  20. Kappas A, Drummond GS, Manola T, Petmezaki S, Valaes T: Sn-protoporphyrin use in the management of hyperbilirubinemia in term newborns with direct Coombs-positive ABO incompatibility. Pediatrics 1988;81:485–497.
  21. Valaes T, Petmezaki S, Henschke C, Drummond GS, Kappas A: Control of jaundice in preterm newborns by an inhibitor of bilirubin production: studies with tin-mesoporphyrin. Pediatrics 1994;93:1–11.
  22. Reddy P, Najundaswamy S, Mehta R, Petrova A, Hegyi T: Tin-mesoporphyrin in the treatment of severe hyperbilirubinemia in a very-low-birth-weight infant. J Perinatol 2003;23:507–508.
  23. Kappas A, Drummond GS, Munson DP, Marshall JR: Sn-Mesoporphyrin interdiction of severe hyperbilirubinemia in Jehovah’s Witness newborns as an alternative to exchange transfusion. Pediatrics 2001;108:1374–1377.
  24. Kappas A: A method for interdicting the development of severe jaundice in newborns by inhibiting the production of bilirubin. Pediatrics 2004;113:119–123.
  25. Lin CH, Lo WC, Hsiao M, Tung CS, Tseng CJ: Interactions of carbon monoxide and metabotropic glutamate receptor groups in the nucleus tractus solitarii of rats. J Pharmacol Exp Ther 2004;308:1213–1218.
  26. Watkins CC, Boehning D, Kaplin AI, Rao M, Ferris CD, Snyder SH: Carbon monoxide mediates vasoactive intestinal polypeptide-associated nonadrenergic/noncholinergic neurotransmission. Proc Natl Acad Sci USA 2004;101:2631–2635.
  27. Koehler RC, Traystman RJ: Cerebrovascular effects of carbon monoxide. Antioxid Redox Signal 2002;4:279–290.
  28. Hoekstra KA, Godin DV, Cheng KM: Protective role of heme oxygenase in the blood vessel wall during atherogenesis. Biochem Cell Biol 2004;82:351–359.
  29. Ryter SW, Otterbein LE, Morse D, Choi AM: Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance. Mol Cell Biochem 2002;234–235:249–263.
  30. Dennery PA, McDonagh AF, Spitz DR, Rodgers PA, Stevenson DK: Hyperbilirubinemia results in reduced oxidative injury in neonatal Gunn rats exposed to hyperoxia. Free Radic Biol Med 1995;19:395–404.
  31. Zhang W, Contag PR, Hardy J, Zhao H, Vreman HJ, Hajdena-Dawson M, Wong RJ, Stevenson DK, Contag CH: Selection of potential therapeutics based on in vivo spatiotemporal transcription patterns of heme oxygenase-1. J Mol Med 2002;80:655–664.
  32. Morioka I, Wong RJ, Abate A, Vreman HJ, Contag CH, Stevenson DK: Systemic effects of orally administered metalloporphyrins on heme oxygenase expression in mice. PAS 2005;57:1273.
  33. Vreman HJ, Lee OK, Stevenson DK: In vitro and in vivo characteristics of a heme oxygenase inhibitor: ZnBG. Am J Med Sci 1991;302:335–341.
  34. Vreman HJ, Zentner AR, Wong RJ, Stevenson DK: Carbon monoxide production and upregulation of heme oxygenase activity in mice after heme administration. Pediatr Res 1999;45:231A.

    External Resources

  35. Contag CH, Contag PR, Mullins JI, Spilman SD, Stevenson DK, Benaron DA: Photonic detection of bacterial pathogens in living hosts. Mol Microbiol 1995;18:593–603.
  36. Vreman HJ, Stevenson DK: Detection of heme oxygenase activity by measurement of CO; in Maines MD, Costa LG, Reed DJ, et al (eds): Current Protocols in Toxicology. New York, NY, John Wiley & Sons, 1999, pp 9.2.1–9.2.10.
  37. Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970;227:680–685.
  38. Towbin H, Staehelin T, Gordon J: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. 1979. Biotechnology 1992;24:145–149.
  39. Dennery PA, Sridhar KJ, Lee CS, Wong HE, Shokoohi V, Rodgers PA, Spitz DR: Heme oxygenase-mediated resistance to oxygen toxicity in hamster fibroblasts. J Biol Chem 1997;272:14937–14942.
  40. Wong RJ, Nguyen XN, Zhao H, Vreman HJ, Contag CH, Stevenson DK: Developmentally regulated pattern of heme oxygenase-1 expression in the mouse brain. Pediatr Res 2002;51:328A.
  41. Wong RJ, Morioka I, Vreman HJ, Stevenson DK: Oral absorptivity of tin mesoporphyrin (SnMP) and distribution into the brain of young mice. PAS 2005;57:1277.