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Published on: March 22, 2016
Oxidative stress and oxidative DNA damage is characteristic for mixed Alzheimer disease/vascular dementia
Daniel Gackowski1, Rafal Rozalski, Agnieszka Siomek
1Department of Clinical Biochemistry, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Karlowicza 24, 85-092 Bydgoszcz, Poland.
Abstract:
Oxidative DNA damage may contribute to neuronal cell loss and may be involved in pathogenesis of some neurodegenerative diseases. We assessed the broad spectrum of oxidative DNA damage biomarkers and antioxidants in mixed Alzheimer disease/vascular dementia (MD) and in control patients. The amount of the products of oxidative DNA damage repair (8-oxo-2'-deoxyguanosine and 8-oxoguanine) excreted into urine and cerebrospinal fluid (CSF) was measured by gas chromatography/mass spectrometry with HPLC pre-purification. The level of 8-oxo-2'-deoxyguanosine in leukocytes' DNA, antioxidant vitamins and uric acid concentrations in blood plasma were analyzed by the mean of HPLC technique. For the first time we demonstrated oxidative DNA damage on the level of whole organism and in CSF of MD patients. Urinary excretion of oxidative DNA damage repair products were higher in patients with MD than in the control group. The level 8-oxoguanine in cerebrospinal fluid of MD patients almost doubled the level found in the control group. Also the concentrations of ascorbic acid and retinol in plasma were reduced in MD patients. Oxidative stress/DNA damage is an important factor that may be involved in pathogenesis of mixed dementia. It is likely that treatment of these patients with antioxidants may slow down the progression of the disease.
Insights
Oxidative DNA damage is elevated in patients with mixed dementia (MD). This suggests oxidative stress plays a role in MD pathogenesis, and antioxidants may help slow disease progression.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Oxidative DNA damage is implicated in neuronal loss and neurodegenerative disease pathogenesis.
- Assessing oxidative DNA damage biomarkers and antioxidants is crucial for understanding dementia.
Purpose of the Study:
- To evaluate oxidative DNA damage biomarkers and antioxidants in mixed dementia (MD) patients.
- To investigate the role of oxidative stress in the pathogenesis of MD.
Main Methods:
- Measured urinary and cerebrospinal fluid (CSF) oxidative DNA damage repair products (8-oxo-2'-deoxyguanosine, 8-oxoguanine) using gas chromatography/mass spectrometry.
- Analyzed leukocyte DNA 8-oxo-2'-deoxyguanosine, plasma antioxidant vitamins, and uric acid via HPLC.
Main Results:
- Demonstrated significant oxidative DNA damage in MD patients at the organism and CSF levels.
- Excretion of oxidative DNA damage repair products was higher in MD patients.
- CSF 8-oxoguanine levels nearly doubled in MD patients compared to controls.
- MD patients showed reduced plasma concentrations of ascorbic acid and retinol.
Conclusions:
- Oxidative stress and DNA damage are significant factors in the pathogenesis of mixed dementia.
- Antioxidant therapy may potentially slow the progression of mixed dementia.
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