Difluoromethylornithine decreases long-lasting protein oxidation induced by neonatal ethanol exposure in the hippocampus of adolescent rats.
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.
Mello
Carlos Fernando
CF
Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, Santa Maria, Brazil.
Rubin
Maribel Antonello
MA
Sultana
Rukhsana
R
Barron
Susan
S
Littleton
John Martin
JM
Butterfield
D Allan
DA
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015317:Biogenic Polyamines / Q000096:biosynthesis; D001923:Brain Chemistry / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity*; D000518:Eflornithine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000447:Aldehydes; D015317:Biogenic Polyamines; D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D065108:Ornithine Decarboxylase Inhibitors; C002744:3-nitrotyrosine; D000431:Ethanol; D014443:Tyrosine; C027576:4-hydroxy-2-nonenal; D000518:Eflornithine