First-in-human study demonstrating pharmacological activation of heme oxygenase-1 in humans

Clin Pharmacol Ther. 2010 Feb;87(2):187-90. doi: 10.1038/clpt.2009.221. Epub 2009 Dec 2.

Abstract

Heme oxygenase (HO)-1 degrades heme and protects against oxidative stress, but it has not been pharmacologically induced in humans. In this randomized study of 10 healthy volunteers, hemin (3 mg/kg intravenously in 25% albumin) was shown to increase plasma HO-1 protein concentration four- to fivefold and HO-1 activity ~15-fold relative to baseline at 24 and 48 h (placebo -56.41 +/- 6.31 (baseline), 69.79 +/- 13.00 (24 h), 77.44 +/- 10.62 (48 h) vs. hemin -71.70 +/- 9.20 (baseline), 1,126.20 +/- 293.30 (24 h), 1,192.20 +/- 333.30 (48 h)) in four of five subjects as compared with albumin alone (P </= 0.03). This represents the overcoming of a fundamental hurdle to HO-1 research in humans.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Enzyme Activation / drug effects
  • Enzyme Induction / drug effects
  • Female
  • Heme Oxygenase-1 / blood
  • Heme Oxygenase-1 / drug effects*
  • Heme Oxygenase-1 / metabolism
  • Hemin / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Serum Albumin / chemistry*
  • Young Adult

Substances

  • Serum Albumin
  • Hemin
  • Heme Oxygenase-1