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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


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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.
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