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IS-039 Antioxidant Strategies: Where Are We Now?
  1. F van Bel
  1. Neonatology, University Medical Center Utrecht, Utrecht, Netherlands

Abstract

Part of asphyxia-related brain damage occurs upon reoxygenation. Renewed availability of oxygen activate biochemical pathways and neuronal cell death. Important pathways are: 1) Calcium-induced formation of neurotransmitters; 2) formation of (pro-) radicals; 3) activation of inflammation; 4) induction of apoptosis; 5) depletion of growth factors. Four important sources of free radicals are: 1) Nitric oxide (NO)-related formation of peroxynitrite. It is reported that selective iNOS/eNOS inhibitor 2-iminobiotin induced neuroprotection after asfyxia in animal models. 2) Pro-radicals, such as non proteinbound-iron (NPBI), lead to formation of hydroxyl free radicals. NPBI chelation with deferoxamine, which has also a stabilising effect on HIF1-alpha and stimulates trophic factors, showed encouraging results in experimental models. 3) Formation of superoxide radical by metabolisation by xanthine-oxidase (XO) can be blocked by XO-inhibitors such as allopurinol. 4) Metabolisation of arachidonic acid to prostaglandin leading to superoxide can be blocked by cyclo-oxygenase inhibitors. Since XO-derived superoxide occurs upon reoxygenation after asphyxia, a trial with allopurinol to the mother with signs of perinatal fetal hypoxia has been started. Activation of inflammatory factors after asphyxia is recognised to be related to post-aphyxial brain damage.

Rather than monotherapy directed to one pathway, a combination of drugs intervening in various pathways in relation with the time-profile of these pathways, might achieve optimal reduction of reperfusion injury.

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