Influence of vitamin E, sodium selenite, and astrocyte-conditioned medium on neuronal survival after chronic exposure to ethanol.
Free radicals species generation during ethanol metabolism is implicated in ethanol-induced toxicity. Findings from clinical studies have clearly established the association between alcohol intake and nutritional deficiency. Astrocytes are able to promote neuronal survival against different lethal injuries involved in ethanol-induced toxicity. We therefore studied the ability of hydrosoluble vitamin E (trolox), sodium selenite, and astrocyte-conditioned medium to protect cultured rat neurones against ethanol-induced oxidative stress after chronic exposure to ethanol. When a 6-day exposure to ethanol (20 mM) led to a loss of cell viability, the presence of trolox (10 microM) offered a significant neuroprotection. In the presence of 3-amino-1,2,4-triazole, a catalase inhibitor that created conditions that were favorable to reactive oxygen species accumulation, trolox was able to counteract the deleterious effect of the inhibitor. Moreover, flow cytometric analysis indicated that trolox can maintain the intracellular glutathione content in neurones chronically exposed to ethanol. In these conditions of exposure, the absence of sodium selenite in the culture medium significantly aggravated the exposure-induced effects, whereas sodium selenite (100 nM) offered a significant neuroprotection. Finally, the presence of 25% astrocyte-conditioned medium in the neuronal culture medium induced a neuroprotective effect in the presence of ethanol. Nevertheless, when astrocytes were previously chronically (3 days) exposed to ethanol, their culture medium did not offer a significant protection. These results evidenced that vitamin E and astrocytes can protect neurones from ethanol-induced oxidative stress, notably by contributing to maintaining the intracellular glutathione levels. Selenium, by means of its exogenous addition in the form of sodium selenite, also had an interesting neuroprotective effect.
Lamarche
Frédéric
F
Laboratoire Oligo-éléments et Résistance au Stress Oxydant induit par les Xénobiotiques, Faculté de Médecine de Grenoble, Domaine de la Merci, 38706 La Tronche Cedex, France.
Signorini-Allibe
Nathalie
N
Gonthier
Brigitte
B
Barret
Luc
L
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001253:Astrocytes / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D002492:Central Nervous System Depressants; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D014810:Vitamin E; D000431:Ethanol; D005978:Glutathione; D018038:Sodium Selenite; D000640:Amitrole