Haem arginate infusion stimulates haem oxygenase-1 expression in healthy subjects.
OBJECTIVE
Haem oxygenase 1 (HO-1) is an inducible protein that plays a major protective role in conditions such as ischaemia-reperfusion injury and inflammation. In this study, we have investigated the role of haem arginate (HA) in human male subjects in the modulation of HO-1 expression and its correlation with the GT length polymorphism (GT(n)) in the promoter of the HO-1 gene.


METHODS
In a dose-escalation, randomized, placebo-controlled trial, seven healthy male subjects with a homozygous short (S/S) and eight with a long (L/L) GT(n) genotype received intravenous HA. HO-1 protein expression and mRNA levels in peripheral blood monocytes, bilirubin, haptoglobin, haemopexin and haem levels were analysed over a 48 h observation period.


RESULTS
We found that the baseline mRNA levels of HO-1 were higher in L/L subjects, while protein levels were higher in S/S subjects. HA induced a dose-dependent increase in the baseline corrected area under the curve values of HO-1 mRNA and protein over 48 h. The response of HO-1 mRNA was more pronounced in L/L subjects but the protein level was similar across the groups.


CONCLUSIONS
HA is an effective inducer of HO-1 in humans irrespective of the GT(n) genotype. The potential therapeutic application of HA needs to be evaluated in clinical trials.
Doberer
D
D
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Haschemi
A
A
Andreas
M
M
Zapf
T-C
TC
Clive
B
B
Jeitler
M
M
Heinzl
H
H
Wagner
O
O
Wolzt
M
M
Bilban
M
M
D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001663:Bilirubin / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D006242:Haptoglobins / Q000378:metabolism; D006418:Heme / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D006466:Hemopexin / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011110:Polymorphism, Genetic
D006242:Haptoglobins; D006418:Heme; D006466:Hemopexin; D001120:Arginine; D051547:Heme Oxygenase-1; C048849:heme arginate; D001663:Bilirubin