Ethanol can modify the effects of certain free radical-generating systems on astrocytes.
The central nervous system is vulnerable to oxidative stress, especially when a toxicant can modify the physiological balance between anti- and pro-oxidant mechanisms. Among brain cells, astrocytes seem less vulnerable than neurons, but their impairment can dramatically affect neurons because of their protective role toward neurons. Ethanol is able to stimulate the formation of reactive oxygen species and modify the activity of most of the antioxidant agents. However, ethanol can react with the OH* radical to form the alpha-hydroxyethyl radical, which is considered to be less toxic. Ethanol also can stimulate H2O2 degradation through catalase activation. This study, therefore, sought to determine whether ethanol affected the sensitivity of astrocytes exposed to various free radical-generating systems. The cellular impact of such exposure was assessed by assays exploring cytotoxicity (i.e., NR (neutral red) and MMT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetiazolium bromide) reduction assays) and genotoxicity (comet assay) induced by these treatments. DNA alterations were evaluated by single-cell gel electrophoresis (comet assay), considered a precocious biomarker of intracellular alterations. After concomitant exposure to H2O2 and ethanol, the viability of astrocytes decreased significantly whereas the mean percentage of DNA in the tail increased,reflecting DNA damage (H2O2 was either directly added to the culture medium or endogenously produced from menadione). Ethanol also reduced the loss of viability and DNA alterations after exposure to OH* radicals produced by a Fenton system. The exposure to a xanthine/xanthine oxidase system had the same effect.
Gonthier
B
B
Laboratoire ORSOX (Oligoéléments et Résistance au Stress Oxydant induit par les Xénobiotiques) UMR UJF/CEA-LCR CEA 8M, Université Joseph Fourier, La Tronche, France.
Signorini-Allibe
N
N
Soubeyran
A
A
Eysseric
H
H
Lamarche
F
F
Barret
L
L
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004622:Embryo, Mammalian; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D005609:Free Radicals; D000431:Ethanol; D004247:DNA; D006861:Hydrogen Peroxide