Abstract
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 GM 1 (AGF 2) 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.
Highlights
The toxicity of ethanol has been in part attributed to its ability to promote lipid peroxidation and other indices of oxidative stress [I 0,29,31]
Levels of ethanol circulating in blood did not differ significantly between groups receiving ethanol alone or ethanol in conjunction with either MK-801 or AGF2, and were 126 ± 23 mg/di
A combination of ethanol with MK-801, profoundly depressed striatal glutathione to values significantly below those obtained with either agent alone (Fig. 4)
Summary
The toxicity of ethanol has been in part attributed to its ability to promote lipid peroxidation and other indices of oxidative stress [I 0,29,31]. While this has been most unequivocally demonstrated in the liver, parallel findings have been reported for the central nervous system of ethanol-treated animals [2,28]. Other targets of ethanol effects in the CNS include inhibition of, followed by upregulation of, the NMDA receptor for glutamate [11, 19,38] This has led to investigations of the potential of calcium gating glutamate receptors to protect against the adverse excitatory effects of ethanol withdrawal [23].
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