Serum iron increases with acute induction of hepatic heme oxygenase-1 in mice

Drug Metab Rev. 2007;39(2-3):619-26. doi: 10.1080/03602530701468342.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Dihydropyridines / pharmacology
  • Enzyme Induction / drug effects
  • Enzyme Induction / physiology
  • Heme / antagonists & inhibitors
  • Heme / biosynthesis
  • Heme Oxygenase-1 / biosynthesis*
  • Iron / blood*
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Selenium / deficiency

Substances

  • Dihydropyridines
  • diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate
  • Heme
  • Iron
  • Heme Oxygenase-1
  • Selenium