Abstract
Heme oxygenase (HO)-1 is induced by oxidative stress and protects against oxidant injury. We examined the effect of rapid induction of hepatic HO-1 on serum iron level. Serum iron was approximately doubled within 6 h when HO-1 was induced by phenobarbital treatment of selenium-deficient mice. Blocking heme synthesis with diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) prevented the induction of HO-1 and the rise in serum iron. DDC did not block HO-1 induction by hemin. Inhibition of HO activity by tin protoporphyrin prevented a rise in serum iron that occurred following phorone treatment. These results indicate that heme synthesis or an exogenous source of heme is needed to allow induction of HO-1. Further, they link HO-1 induction with a rise in serum iron, suggesting that the iron resulting from catabolism of heme by HO-1 is released by the liver.
Original language | English (US) |
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Pages (from-to) | 619-626 |
Number of pages | 8 |
Journal | Drug Metabolism Reviews |
Volume | 39 |
Issue number | 2-3 |
DOIs | |
State | Published - Apr 2007 |
Externally published | Yes |
Keywords
- Heme
- Heme oxygenase-1
- Heme synthesis
- Iron export
- Oxidative stress
- Selenium deficiency
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmacology (medical)