Free iron, total F-isoprostanes and total F-neuroprostanes in a model of neonatal hypoxic-ischemic encephalopathy: neuroprotective effect of melatonin.
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.
Signorini
Cinzia
C
Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, Siena, Italy. signorini2@unisi.it
Ciccoli
Lucia
L
Leoncini
Silvia
S
Carloni
Silvia
S
Perrone
Serafina
S
Comporti
Mario
M
Balduini
Walter
W
Buonocore
Giuseppe
G
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D028441:F2-Isoprostanes / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000517:prevention & control*; D007501:Iron; D008550:Melatonin / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats
D000975:Antioxidants; D028441:F2-Isoprostanes; D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids; D007501:Iron; D008550:Melatonin