Systemic effects of orally-administered zinc and tin (IV) metalloporphyrins on heme oxygenase expression in mice

Pediatric Research
Ichiro MoriokaDavid K Stevenson

Abstract

Some metalloporphyrins (Mps) inhibit heme oxygenase (HO), the rate-limiting enzyme in the production of bilirubin, and are potential compounds for the treatment of neonatal jaundice. We studied the safety and efficacy of Mps following oral administration. Adult HO-1-luc reporter mice were administered 30 micromol/kg body weight of tin mesoporphyrin (SnMP), zinc bis glycol deuteroporphyrin (ZnBG), or zinc protoporphyrin (ZnPP), or vehicle by oral gavage. Bilirubin production was measured as total body carbon monoxide (CO) excretion (VeCO). HO activity was quantitated via CO measurements by gas chromatography. HO-1 protein was determined by Western blot. HO-1 transcription levels were assessed by in vivo bioluminescence imaging. A significant 28% decrease in bilirubin production occurred within 3 h of SnMP treatment and persisted beyond 48 h. Bilirubin production decreased 15% and 9% by 3 h after administration of ZnBG and ZnPP, respectively, but returned to baseline within 48 h. Maximal inhibition of liver, spleen, and intestine HO activity was seen at 3 h with inhibitory effects decreasing in the order: SnMP > or = ZnBG > or = ZnPP. After SnMP treatment, HO-1 transcription increased 5.7-fold after 24 h. Furthermore, liver and s...Continue Reading

References

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Mar 13, 2002·Archives of Biochemistry and Biophysics·Ying ShanHerbert L Bonkovsky
Oct 24, 2002·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Weisheng ZhangChristopher H Contag
Sep 19, 2003·Journal of Perinatology : Official Journal of the California Perinatal Association·Pradeep ReddyThomas Hegyi

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Citations

May 15, 2012·Pediatric Research·Stephanie SchulzDavid K Stevenson
Jun 26, 2008·Antioxidants & Redox Signaling·Agnieszka LobodaJozef Dulak
Sep 13, 2006·Pediatric Research·Hui ZhaoChristopher H Contag
Jul 26, 2011·Pediatric Research·Cynthia X HeDavid K Stevenson
Sep 29, 2007·Canadian Journal of Physiology and Pharmacology·Lucie MuchovaDavid K Stevenson
Sep 2, 2008·Canadian Journal of Physiology and Pharmacology·Robert T KinobeKanji Nakatsu
Oct 9, 2008·Canadian Journal of Physiology and Pharmacology·Takeshi MorisawaDavid K Stevenson
Aug 3, 2010·Pediatrics and Neonatology·Ronald S CohenDavid K Stevenson
Jun 7, 2011·Seminars in Perinatology·David K StevensonRonald J Wong
Dec 17, 2009·Seminars in Fetal & Neonatal Medicine·David K Stevenson, Ronald J Wong
Mar 5, 2016·Journal of Perinatology : Official Journal of the California Perinatal Association·V K BhutaniM J Maisels
Jan 30, 2007·Biochemical and Biophysical Research Communications·Aida AbateDavid K Stevenson
Mar 13, 2012·Cell Metabolism·Houman AshrafianHugh Watkins
Dec 21, 2007·Biology of Reproduction·Hui ZhaoDavid K Stevenson
Jun 28, 2018·Molecular Neurobiology·Ignazio BarbagalloDaniele Tibullo
Sep 20, 2017·Neonatology·Stephanie KourulaDavid K Stevenson

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