Difluoromethylornithine decreases long-lasting protein oxidation induced by neonatal ethanol exposure in the hippocampus of adolescent rats

Carlos Fernando Mello, Maribel Antonello Rubin, Rukhsana Sultana, Susan Barron, John Martin Littleton, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: Ethanol exposure and withdrawal during central nervous system development can cause oxidative stress and produce severe and long-lasting behavioral and morphological alterations in which polyamines seem to play an important role. However, it is not known if early ethanol exposure causes long-lasting protein oxidative damage and if polyamines play a role in such a deleterious effect of ethanol. Methods: In this study we investigated the effects of early ethanol exposure (6 g/kg/d, by gavage), from postnatal day (PND) 1 to 8, and of the administration of difluoromethylornithine (DFMO, 500 mg/kg, i.p., on PND 8), a polyamine biosynthesis inhibitor, on the extent of oxidative modification of proteins. Indices of oxidative modification of proteins included protein carbonyls, 3-nitrotyrosine (3-NT), and protein bound 4-hydroxynonenal (HNE) in the hippocampus, cerebellum, hypothalamus, striatum, and cerebral cortex of Sprague-Dawley rats at PND 40. Results: Both ethanol and DFMO administration alone increased protein carbonyl immunoreactivity in the hippocampus at PND 40, but the combination of DFMO and ethanol resulted in no effect on protein carbonyl levels. No alterations in the content of protein-bound HNE, 3-NT, or carbonyl were found in any other cerebral structure. Conclusions: These results suggest that the hippocampus is selectively affected by early ethanol exposure and by polyamine synthesis inhibition. In addition, the results suggest a role for polyamines in the long-lasting increase of protein carbonyls induced by ethanol exposure and withdrawal. ©

Original languageEnglish
Pages (from-to)887-894
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Issue number5
StatePublished - May 2007


  • Alcohol
  • NMDA
  • Oxidative Stress
  • Polyamines
  • Protein Carbonyl

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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