Effect of an NMDA receptor antagonist and a ganglioside GM1 derivative upon ethanol-induced modification of parameters of oxidative stress in several brain regions.
Dietary administration of ethanol to rats for 2 weeks was able to depress levels of glutathione (GSH) and Cu/Zn superoxide dismutase (SOD) in several brain regions. This was indicative of the generation of excess levels of reactive oxygen in treated animals. The potentially protective effect of both an NMDA receptor blocker (MK-801) and an internally esterified derivative of ganglioside GM1 (AGF2) upon ethanol-induced changes in these indices of oxidative stress, was studied. Both of these agents are reported to have neuroprotective properties, but neither was able to prevent ethanol-induced reduction of GSH and SOD levels in any brain area studied. In fact, both agents depressed SOD and GSH levels in midbrain independently of ethanol. MK-801 had a pronounced pro-oxidant potential, and when administered in combination with ethanol. GSH and SOD were reduced in midbrain and striatum to levels below those obtained with either agent alone. The pro-oxidant properties of ethanol may thus act independently of its actions upon the NMDA receptor. The protective properties of NMDA receptor inhibitors or gangliosides cannot be attributed to any antioxidant effect.
Bondy
S C
SC
Department of Community and Environmental Medicine, University of California, Irvine 92717-1825, USA.
Guo
S X
SX
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004032:Diet; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013482:Superoxide Dismutase / Q000378:metabolism
D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D005677:G(M1) Ganglioside; D000431:Ethanol; D016291:Dizocilpine Maleate; D013482:Superoxide Dismutase; D005978:Glutathione