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Randomized Controlled Trial
. 2010 Feb;87(2):187-90.
doi: 10.1038/clpt.2009.221. Epub 2009 Dec 2.

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

A E Bharucha  1 , A Kulkarni, K M Choi, M Camilleri, M Lempke, G J Brunn, S J Gibbons, A R Zinsmeister, G Farrugia
Affiliations
Randomized Controlled Trial

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

A E Bharucha et al. Clin Pharmacol Ther. 2010 Feb.

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.

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Conflict of interest statement

CONFLICT OF INTEREST/DISCLOSURE

There are no conflicts or disclosures pertaining to this manuscript.

Figures

Figure 1
Figure 1
Effect of hemin and placebo on venous plasma HO-1 protein concentrations plotted for each participant. Hemin increased HO-1 protein concentrations in 4 of 5 volunteers. However, placebo (albumin) did not increase HO-1 in any subjects.
Figure 2
Figure 2
Effect of hemin and placebo on venous plasma HO-1 activity plotted for each participant. Only, hemin and not placebo substantially increased HO-1 activity, i.e., in the same 4 volunteers in whom hemin increased HO-1 protein. The exception was subject A (see text), in whom venous plasma HO-1 protein concentration increased from 1.8 to 3.0 ng/mL while activity increased from 43 to 129 pmol bilirubin/mg/h.
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