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

被引：63

作者：

Bharucha, A. E. ^{[1
]}

Kulkarni, A. ^{[1
]}

Choi, K. M. ^{[1
]}

Camilleri, M. ^{[1
]}

Lempke, M.

Brunn, G. J. ^{[2
]}

Gibbons, S. J. ^{[1
]}

Zinsmeister, A. R. ^{[2
]}

Farrugia, G. ^{[1
]}

机构：

[1] Mayo Clin & Mayo Fdn, Div Gastroenterol & Hepatol, Enter Neurosci Program, Rochester, MN 55905 USA

[2] Mayo Clin & Mayo Fdn, Div Biomed Stat & Informat, Rochester, MN 55905 USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2010年 / 87卷 / 02期

基金：

美国国家卫生研究院;

关键词：

MYELODYSPLASTIC SYNDROMES; UP-REGULATION; INTRAVENOUS HEMATIN; DISEASE; INDUCTION; ARGINATE; MONOXIDE; KIDNEY; RATS;

D O I：

10.1038/clpt.2009.221

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 similar to 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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收藏

页码：187 / 190

页数：4

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