First-in-Human Study Demonstrating Pharmacological Activation of Heme Oxygenase-1 in Humans

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 fivefol...

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Published in:Clinical pharmacology and therapeutics 2010-02, Vol.87 (2), p.187-190
Main Authors: Bharucha, A E, Kulkarni, A, Choi, K M, Camilleri, M, Lempke, M, Brunn, G J, Gibbons, S J, Zinsmeister, A R, Farrugia, G
Format: Article
Language:English
Subjects:
Adolescent
Adult
Biological and medical sciences
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
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Serum Albumin - chemistry
Young Adult
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Summary: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. Clinical Pharmacology & Therapeutics (2010) 87 2, 187–190. doi:10.1038/clpt.2009.221
ISSN:0009-9236
1532-6535
DOI:10.1038/clpt.2009.221