Casper Møller Frederiksen and Jørgen Clausen

It has been suggested that glial cells in the central nervous system might function as a buffer and protect neurons and synapses. Associated with such a function, glial cells might be affected in degenerative diseases, for example, Alzheimer’s disease and Parkinson’s disease, due to generation of free-radicals. Free-radicals might be generated during the metabolic
transformation of xenobiotics. The purpose of the present study was to determine whether a xenobiotic (in this case, paraquat), is metabolised in glial cells during the generation of freeradicals. Furthermore, this study determined whether free-radicals can induce DNA fragmentation and whether this fragmentation can be repaired. The data produced indicated that astroglial cells contain P450-reductase which transforms paraquat into a pyridium free-radical. In turn, this causes a dose-dependent DNA fragmentation, as determined by using single-cell gel electrophoresis. The dose-dependent effect was valid up to 80μM paraquat. The oxidative stress induced in the astroglial cells was also associated with a maximum 15% increase in the anti-oxidative enzyme, glutathione peroxidase. After exposure to 40μM paraquat, followed by growth of the cells in a paraquat-free medium, DNA repair was shown to be rather slow, and was only obvious two hours after exposure to paraquat. This might be related the shuttle in which paraquat/P450-reductase is implicated, which causes a protracted generation of free-radicals. The data are discussed in relation to the available literature.
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