The serum protein and lipid oxidation marker levels in Alzheimer's disease and effects of cholinesterase inhibitors and antipsychotic drugs therapy.
Oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to evaluate the serum oxidation marker levels in patients with AD. Both untreated patients (n: 15) and patients who received treatment (n: 62) had higher Malondialdehyde (p<0.01 and p<0.001), Oxidized LDL (ox-LDL; p<0.0001 and p<0.0001), F(2)-isoprostane (p<0.0001 and p<0.001), and Nitric oxide (NOx; p<0.0001 and p<0.0001) levels compared with those of age-matched controls (n: 15). Protein Carbonyl and Asymmetrical Dimethyl-L-Arginine levels in Alzheimer patients were not found to be different from the controls. Short-term cholinesterase inhibitor (ChEIs) therapy (7, 5 +/-1, 5 months, n: 12) resulted in a reduction in ox-LDL and NOx levels (p<0.05 and p<0.01) from baseline. Long-term ChEI- therapy group (50, 4+/- 30, 5 months, n: 33) has higher ox-LDL, NOx and F(2)-isoprostane levels than short-term treated group (p<0.01, p<0.001 and p<0.05, respectively). Ox-LDL levels were also found to be lower in ChEI patients who were given antipsychotic treatment (n: 15) than in the group who were ChEIs-alone treatment group (p<0.0001). MMSE scores showed negative correlation with both NOx (p<0.05) and ox-LDL (p<0.05) levels. There was positive correlation between NOx and both MDA (p<0.05) and ox-LDL (p<0.05), and between F(2)-isoprostane and 3-NT (p<0.05). In conclusion, our results suggest that serum NOx-induced lipid oxidation levels were increased in AD and use of antipsychotic drugs may cause lower ox-LDL levels in patients having combination therapy with ChEi's. However, it is required further studies for the determination of clinical importance of these markers.
Sinem
F
F
Department of Biochemistry, Istanbul University, Istanbul, Turkey.
Dildar
K
K
Gökhan
E
E
Melda
B
B
Orhan
Y
Y
Filiz
M
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000188:drug therapy; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*
D014150:Antipsychotic Agents; D015415:Biomarkers; D001798:Blood Proteins; D008078:Cholesterol, LDL; D002800:Cholinesterase Inhibitors; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein