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Doberer, D; Haschemi, A; Andreas, M; Zapf, T‐C; Clive, B; Jeitler, M; Heinzl, H; Wagner, O; Wolzt, M; Bilban, M.
British journal of pharmacology, December 2010, Letnik: 161, Številka: 8Journal Article
BACKGROUND AND PURPOSE 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 (GTn) in the promoter of the HO‐1 gene. EXPERIMENTAL APPROACH 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) GTn 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. KEY 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 AND IMPLICATION HA is an effective inducer of HO‐1 in humans irrespective of the GTn genotype. The potential therapeutic application of HA needs to be evaluated in clinical trials.
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