Abstract | BACKGROUND: 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.
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Authors | Glenn H DeSandre, Ronald J Wong, Ichiro Morioka, Christopher H Contag, David K Stevenson |
Journal | Biology of the neonate
(Biol Neonate)
Vol. 89
Issue 3
Pg. 139-46
( 2006)
ISSN: 0006-3126 [Print] Switzerland |
PMID | 16205054
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright (c) 2006 S. Karger AG, Basel. |
Chemical References |
- Metalloporphyrins
- tin mesoporphyrin
- Heme
- Carbon Monoxide
- Heme Oxygenase-1
- Bilirubin
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Topics |
- Animals
- Bilirubin
(biosynthesis)
- Carbon Monoxide
(analysis)
- Disease Models, Animal
- Heme
(administration & dosage)
- Heme Oxygenase-1
(analysis, genetics, metabolism)
- Hyperbilirubinemia
(prevention & control)
- Metalloporphyrins
(therapeutic use)
- Mice
- Mice, Transgenic
- Transcription, Genetic
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