Oxidative stress due to
free radical formation and initiation of abnormal oxidative reactions is involved in several diseases of newborns, such as
hypoxic-ischemic encephalopathy.
Melatonin, an endogenously produced indoleamine primarily formed in the pineal gland, is a potent
free radical scavenger as well as an indirect
antioxidant. The present study was conducted to evaluate the formation of oxidative damage mediators and the possible effect of
melatonin treatment in a model of
hypoxic-ischemic encephalopathy in 7-day-old rats. Pups were subjected to permanent
ligation of the right common carotid artery and exposed for 2.5 hr to a
nitrogen-
oxygen mixture (92% and 8%, respectively) (
hypoxia-
ischemia, HI).
Melatonin was injected intraperitoneally to a group of rats at the dose of 15 mg/kg 30 min before starting the ischemic procedure (HI-
Melatonin). After 24 hr of treatment, in homogenized cerebral cortex, desferoxamine (DFO)-chelatable free
iron, total F(2)-isoprostanes and total F(4)-neuroprostanes, originating from the
free radical-catalyzed peroxidation of arachidonic and
docosahexaenoic acids, respectively, were determined. HI induced a significant increase in DFO-chelatable
iron, total F(2)-isoprostanes and F(4)-neuroprostanes in both right and left side of the cerebral cortex. In HI-
Melatonin-treated animals the levels of free
iron, F(2)-isoprostanes, and F(4)-neuroprostanes were significantly lower than that in HI rats and the values were similar to controls. These data show the important neuroprotective role of
melatonin in reducing oxidative damage resulting from HI.
Melatonin could represent a potential safe approach to perinatal brain damage in humans.