- •Oxidative stress is one of the major contributory factor in AD pathogenesis.
- •GSH/GSSG ratio is an important determinant for susceptibility of DNA to oxidation.
- •DNA damage parameters were higher in AD patients.
- •Memantine may decreases DNA strand breaks and DNA susceptibility to oxidation but not oxidation of purines.
The aim of the current study was to compare oxidative DNA damage, DNA susceptibility to oxidation, and ratio of GSH/GSSG in patients with Alzheimer's disease (AD) treated with acetylcholinesterase inhibitor (AChEI) and combined AChEI + memantine. The study included 67 patients with AD and 42 volunteers as control. DNA damage parameters (strand breaks, oxidized purines, H2O2-induced DNA damage) in lymphocyte DNA and GSH/GSSG ratio in erythrocytes were determined by the comet assay and spectrophotometric assay, respectively. DNA damage was found to be higher, GSH/GSSG ratio was found to be lower in the AD group than those in the control group. DNA strand breaks and H2O2-induced DNA damage were lower in the patients taking AChEI + memantine than those in the patients taking AChEI but no significant difference was determined between the groups for oxidized purines and GSH/GSSG ratio. In conclusion, increased systemic oxidative DNA damage and DNA susceptibility to oxidation may be resulted from diminished GSH/GSSG ratio in AD patients. Although DNA strand breaks and H2O2-induced DNA damage are lower in the AD patients treated with combined AChEI and memantine, this may not indicate protective effect of memantine against DNA oxidation due to similar levels of oxidized purines in the patients treated with AChEI and AChEI + memantine.
Abbreviations:Aβ (amyloid β-peptide), AChEI (acetylcholine esterase inhibitor), AD (Alzheimer's disease), BMI (body mass index), GSH (glutathione), GSSG (oxidized glutathione), hOGG1 (human 8-oxoguanine DNA glycosylase 1), MMSE (mini-mental state examination), NMDA (N-methyl-d-aspartate), RNS (reactive nitrogen species), ROS (reactive oxygen species), 8-OHdG (8-hydroxydeoxyguanosine)
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Published online: April 29, 2017
Accepted: April 28, 2017
Received in revised form: March 31, 2017
Received: February 6, 2017
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