Desferrioxamine enhances hypoxic ventilatory response and induces tyrosine hydroxylase gene expression in the rat brainstem in vivo
J of Neuroscience Research. 2007-02-15; 85(5): 1119-1125
DOI: 10.1002/jnr.21202
Lire sur PubMed
The iron chelator desferrioxamine (DFO) induces accumulation of the hypoxia‐inducible factor (HIF‐1), a transcription factor that up‐regulates genes involved in adaptative responses to hypoxia. This property makes DFO a potential neuroprotector against hypoxic stress. We investigated in rats the effects of DFO on the ventilatory response to mild hypoxic tests and the expression of tyrosine hydroxylase (TH), a target gene of HIF‐1. Two protocols were used, the first with repeated injections of 50 mg/kg DFO every 2 days during a 2‐week period. This was aimed at define the time course of the ventilatory responses to a hypoxic test. In the second protocol, rats were given a single injection of 300 mg/kg DFO. Every day over 4 days, the hypoxic ventilatory response was recorded before the animal was sacrificed, and Western blot analysis of TH in the dorsal brainstem cardiorespiratory area was performed. DFO produced a delayed increase in the hypoxic ventilatory response, which appeared in the same time window as TH up‐regulation (2–3 days after the bolus injection of DFO). This delay suggests a genic effect of the drug that improves the ventilatory response to hypoxia. © 2007 Wiley‐Liss, Inc.