DNA fragmentation

/Tag:DNA fragmentation

The Effects of Oxidative Stress in In Vitro Cultured Astroglial Cells

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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Cytotoxic and Apoptotic Effects on Hepatocytes of Secondary Metabolites Obtained from Lichens

Estela Raquel Correché, Ricardo Daniel Enriz, Marisa Piovano, Juan Garbarino and María José Gómez-Lechón

There are a large number of species of Antarctic lichens, and several studies describing the secondary metabolites present in these lichens, as well as the advances in understanding the chemistry of these metabolites, have been reported. In addition, some derivatives displaying interesting antibacterial effects have been described. The cytotoxic and apoptotic effects of 15 secondary metabolites (depsides, depsidones and usnic acid) obtained from Continental (Chilean) and Antarctic lichens were evaluated in primary cultures of rat hepatocytes. Intracellular lactate dehydrogenase release, caspase 3 activation and DNA fragmentation were measured. In this study, we have evaluated a set of markers associated with pivotal steps in the execution phase of apoptosis, in order to detect compounds with apoptotic effects on hepatocytes before significant necrosis takes place. Flow cytometric analysis of DNA fragmentation revealed an increase in apoptotic nuclei with sub-diploid DNA content after the exposure of hepatocytes to sub-cytotoxic concentrations of the compounds. Among these, salazinic acid, stictic acid and psoromic acid displayed significant apoptotic activities. Divaricatic acid showed only moderate apoptotic effects at sub-cytotoxic concentrations.
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