Grape polyphenols inhibit chronic ethanol-induced COX-2 mRNA expression in rat brain.
BACKGROUND
Chronic ethanol has been shown to increase oxidative stress leading to neurodegenerative changes in the brain. Oxidative stress may up-regulate extracellular signal regulated kinases (ERK1/2) and, subsequently, the arachidonic acid cascade mediated by phospholipase A2 (PLA2) and cyclooxygenase (COX-2). Our earlier study showed that grape polyphenols (GP) could ameliorate oxidative damage to synaptic membrane proteins due to chronic ethanol treatment. This study was aimed at examining the effects of GP on mRNA expression of ERK1/2, cytosolic PLA2 (cPLA2), and COX-2 in different brain regions after chronic ethanol treatment.


METHODS
Male Sprague-Dawley rats were fed a Lieber-DeCarli liquid diet with ethanol or isocaloric amount of maltose, with or without GP for 2 months. In situ hybridization was carried out using coronal brain sections through the hippocampus.


RESULTS
Quantitative in situ hybridization showed no changes in ERK1 and cPLA2 mRNA levels in cortical areas and hippocampus after ethanol and/or GP administration. However, a decrease in ERK2 and an increase in COX-2 mRNA level was found in the hippocampus of ethanol-treated animals. GP completely inhibited the increase in COX-2 due to ethanol treatment.


CONCLUSIONS
Increase in COX-2 expression may be an underlying mechanism for the increase in oxidative stress induced by chronic ethanol administration. Dietary supplementation of GP may have a beneficial role in inhibiting certain alcohol effects.
Simonyi
Agnes
A
Department of Biochemistry, University of Missouri, M121 Medical Sciences Building, Columbia, MO 65212, USA.
Woods
Danielle
D
Sun
Albert Y
AY
Sun
Grace Y
GY
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage*; D005419:Flavonoids; D005786:Gene Expression Regulation / Q000187:drug effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D059808:Polyphenols; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D027843:Vitis
D002492:Central Nervous System Depressants; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D010636:Phenols; D011108:Polymers; D059808:Polyphenols; D012333:RNA, Messenger; D000431:Ethanol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases