title: Protective effects of erythropoietin against ethanol-induced apoptotic neurodegenaration and oxidative stress in the developing C57BL/6 mouse brain.
abstract: The developing central nervous system is extremely sensitive to ethanol, with well-defined temporal periods of vulnerability. Recent studies have shown that administration of ethanol to infant rats during the synaptogenesis period triggers extensive apoptotic neurodegeneration throughout many regions of the developing brain. Furthermore, acute ethanol administration produces lipid peroxidation in the brain as an indicator of oxidative stress. In recent years, it has been shown that erythropoietin (EPO) has a critical role in the development, maintenance, protection, and repair of the nervous system. In the present study, we investigated the effect of EPO against ethanol-induced neurodegeneration and oxidative stress in the developing C57BL/6 mouse brain. Seven-day-old C57BL/6 mice were divided into three groups: control group, saline-treated group, EPO-treated group. Ethanol was administered to mice at a dosage of 2.5 g/kg for two times with a 2-h interval. Recombinant human EPO (rhEPO) was given 1000 U/kg. Twenty-four hours after the first dose of ethanol, all the animals were killed. Neuronal cell death, apoptosis, thiobarbituric acid substance (TBARS) levels, superoxide dismutase (SOD), and glutathione peroxidase (Gpx) enzymes activities were evaluated. Histopathological evaluation demonstrated that EPO significantly diminished apoptosis in the cerebellum, prefrontal cortex, and hippocampus and also spared hippocampal CA1, CA2, and CA3 neurons. Simultaneous administration of EPO along with ethanol attenuated the lipid peroxidation process and restored the levels of antioxidants. Regarding the wide use of erythropoietin in premature newborns, this agent may be potentially beneficial in treating ethanol-induced brain injury in the perinatal period.
authors.affiliation: Department of Pediatrics, School of Medicine, Dokuz Eylul, University, Inciralti, 35340 Izmir, Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Kumral
authors.forename: Kazim
authors.initials: K
authors.lastname: Tugyan
authors.forename: Sevil
authors.initials: S
authors.lastname: Gonenc
authors.forename: Kursat
authors.initials: K
authors.lastname: Genc
authors.forename: Sermin
authors.initials: S
authors.lastname: Genc
authors.forename: Ulker
authors.initials: U
authors.lastname: Sonmez
authors.forename: Osman
authors.initials: O
authors.lastname: Yilmaz
authors.forename: Nuray
authors.initials: N
authors.lastname: Duman
authors.forename: Nazan
authors.initials: N
authors.lastname: Uysal
authors.forename: Hasan
authors.initials: H
authors.lastname: Ozkan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000254:growth & development* / Q000473:pathology; D002452:Cell Count / Q000379:methods; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000097:blood; D004347:Drug Interactions; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D000431:Ethanol / Q000009:adverse effects / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D018696:Neuroprotective Agents; D017392:Thiobarbituric Acid Reactive Substances; D004921:Erythropoietin; D000431:Ethanol; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase