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 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.
Bharucha
A E
AE
Enteric Neurosciences Program, Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA. bharucha.adil@mayo.edu
Kulkarni
A
A
Choi
K M
KM
Camilleri
M
M
Lempke
M
M
Brunn
G J
GJ
Gibbons
S J
SJ
Zinsmeister
A R
AR
Farrugia
G
G
D000293:Adolescent; D000328:Adult; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D051547:Heme Oxygenase-1 / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000737:chemistry*; D055815:Young Adult
D012709:Serum Albumin; D006427:Hemin; D051547:Heme Oxygenase-1