Highlights
- •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.
Abstract
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.
Keywords
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)To read this article in full you will need to make a payment
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References
- Inflammatory hypothesis as a link between Alzheimer's disease and diabetes mellitus.Geriatr. Gerontol. Int. 2016; 16: 1161-1166https://doi.org/10.1111/ggi.12602
- Alzheimer's disease: an insight from epigenetic perspective.in: Dincer Y. Epigenetics Mech. Clin. Perspect. Nova Science Publisher, New York2016: 83-113
- Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain.Transl. Psychiatry. 2012; 2: e134-e138https://doi.org/10.1038/tp.2012.61
- Memantine reduces oxidative damage and enhances long-term recognition memory in aged rats.Neuroscience. 2007; 146: 1719-1725https://doi.org/10.1016/j.neuroscience.2007.03.018
- Protection of DFP-induced oxidative damage and neurodegeneration by antioxidants and NMDA receptor antagonist.Toxicol. Appl. 2009; 240: 124-131https://doi.org/10.1016/j.taap.2009.07.006.Protection
- Diagnostic and Statistical Manual of Mental Disorders.fourth ed. 1994
- Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease.Neurology. 1984; 34: 939-944https://doi.org/10.1212/WNL.34.7.939
- Separation of leukocytes from blood and bone marrow.Scand. J. Clin. Lab. Invest. 1967; 21: 77-89
- Comet assay for determining of DNA damage: review.Türkiye Klin. J. Med. Sci. 2010; 30: 1365-1373
- Folic acid potentiates the effect of memantine on spatial learning and neuronal protection in an alzheimer's disease transgenic model.J. Alzheimers Dis. 2010; 20: 607-615https://doi.org/10.3233/JAD-2010-1396
- NAD attenuates oxidative DNA damages induced by amyloid beta-peptide in primary rat cortical neurons.Free Radic. Res. 2014; 48: 794-805https://doi.org/10.3109/10715762.2014.907889
- Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer's disease.J. Cell Biol. 1998; 143: 777-794
- Clogging of axons by tau, inhibition of axonal traffic and starvation of synapses.Neurobiol. Aging. 2003; 24: 1079-1085
- Increased nuclear DNA oxidation in the brain in Alzheimer's disease.J. Neurochem. 1998; 71: 2034-2040https://doi.org/10.1046/j.1471-4159.1998.71052034.x
- Detection of oxidative DNA damage in lymphocytes of patients with Alzheimer's disease.Biomarkers. 2004; 9: 203-209https://doi.org/10.1080/13547500410001728390
- Oxidative DNA damage in peripheral leukocytes of mild cognitive impairment and AD patients.Neurobiol. Aging. 2005; 26: 567-573https://doi.org/10.1016/j.neurobiolaging.2004.07.016
- DNA methylation landscapes: provocative insights from epigenomics.Nat. Rev. Genet. 2008; 9: 465-476https://doi.org/10.1038/nrg2341
- Epigenetic changes in the progression of Alzheimer's disease.Mech. Ageing Dev. 2013; 134: 486-495https://doi.org/10.1016/j.mad.2013.08.005
- Long interspersed nuclear element-1 hypomethylation and oxidative stress : correlation and bladder cancer diagnostic potential.PLoS One. 2012; 7: e37009https://doi.org/10.1371/journal.pone.0037009
- Glutathione dysregulation and the etiology and progression of human diseases.Biol. Chem. 2009; 390: 191-214https://doi.org/10.1515/BC.2009.033
- Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.Neurobiol. Aging. 2014; 35: 179-190https://doi.org/10.1016/j.neurobiolaging.2013.06.023
- Age-dependent and tissue-related glutathione redox status in a mouse model of Alzheimer's disease.J. Alzheimers Dis. 2012; 28: 655-666https://doi.org/10.3233/JAD-2011-111244
- Peripheral levels of glutathione and protein oxidation as markers in the development of Alzheimer's disease from Mild Cognitive Impairment.Free Radic. Res. 2008; 42: 162-170https://doi.org/10.1080/10715760701861373
- Peripheral markers in neurodegenerative patients and their first-degree relatives.J. Neurol. Sci. 2012; 314: 48-56https://doi.org/10.1016/j.jns.2011.11.001
- Antioxidant status and energy state of erythrocytes in Alzheimer dementia: probing for markers.CNS Neurol. Disord. Drug Targets. 2012; 11: 926-932
- Age-associated decline in gamma-glutamylcysteine synthetase gene expression in rats.Free Radic. Biol. Med. 2000; 28 (pii): 566-574https://doi.org/10.1016/S0891-5849(99)00269-5
- Pharmacological treatment of Alzheimer's disease: is it progressing adequately?.Open Neurol. J. 2009; 3: 27-44
- Memantine lowers amyloid-β peptide levels in neuronal cultures and in APP/PS1 transgenic mice.J. Neurosci. Res. 2010; 88: 143-154https://doi.org/10.1002/jnr.22172.Memantine
- Reduction of phosphorylated tau during memantine treatment of Alzheimer's disease.Dement. Geriatr. Cogn. Disord. 2007; 24: 247-252https://doi.org/10.1159/000107099
- Memantine protects against LPS-induced neuroinflammation, restores behaviorally-induced gene expression and spatial learning in the rat.Neuroscience. 2006; 142: 1303-1315https://doi.org/10.1016/j.neuroscience.2006.08.017
- Neuroprotective effects of memantine in a mouse model of retinal degeneration induced by rotenone.Brain Res. 2008; 11215: 208-217https://doi.org/10.1016/j.brainres.2008.04.001
- Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons.J. Neurochem. 2008; 106: 45-55https://doi.org/10.1111/j.1471-4159.2008.05347.x
- Effects of memantine, a non-competitive N-methyl-D-aspartate receptor antagonist, on genomic stability.Basic Clin. Pharmacol. Toxicol. 2011; 109: 413-417https://doi.org/10.1111/j.1742-7843.2011.00744.x
- Remarkable increase in the concentration of 8-hydroxyguanosine in cerebrospinal fluid from patients with Alzheimer's disease.J. Neurosci. Res. 2002; 70: 447-450https://doi.org/10.1002/jnr.10349
Article info
Publication history
Published online: April 29, 2017
Accepted:
April 28,
2017
Received in revised form:
March 31,
2017
Received:
February 6,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
