The efficacy of donepezil administration on acetylcholinesterase activity and altered redox homeostasis in Alzheimer's disease.

Alzheimer's disease (AD) is a serious multifactorial disorder with progressive neurodegenerative outcomes related with impaired redox homeostasis. Inhibition of the enzyme acetylcholinesterase (AChE), as one of the major therapeutic strategies, is considered to be offering only symptomatic relief and moderate disease modifying effect. We intended to investigate the effects of acetylcholinesterase inhibition via donepezil on protein carbonyl (PCO), advanced protein oxidation products (AOPP) and ischemia modified albumin (IMA) as protein oxidation markers and ferric reducing antioxidant power (FRAP), prooxidant-antioxidant balance (PAB), total thiol (T-SH), protein thiol (P-SH) as antioxidant status markers and also kynurenine (KYN), N-formyl kynurenine (N-FKYN) and protein bound dityrosine (DT) levels all in one demonstrating the redox homeostasis in Alzheimer patients also correlated with AChE activity. The AChE activity and PCO, KYN, N-FKYN and DT levels were found to be significantly higher in the AD group than the control group. The FRAP, T-SH and P-SH levels were significantly lower in the AD group than in the control group. The AChE activity was significantly higher both in donepezil treated and untreated groups when compared with the control group. PCO levels were significantly higher in Alzheimer's untreated group than the healthy control and donepezil treated groups. AChE activity was positively correlated with PCO, IMA, PAB, KYN and N-FKYN levels and negatively correlated with FRAP, T-SH and P-SH levels in all participants. Our data showed that treatment with donepezil had ameliorating effects on redox homeostasis in Alzheimer patients. AChE inhibition seems to be exhibiting a potent antioxidant role and may inhibit protein oxidation by decreasing AChE activity in AD, thus medicinal natural substances exhibiting the similar mechanism of action with their antioxidant behaviours can be recommended for the emphasis on new drug new drug development. Further clinical and experimental studies are needed to support our current findings and conclusions.

Ischemia-modified albumin and advanced oxidation protein products as potential biomarkers of protein oxidation in Alzheimer's disease.

BACKGROUND: The aim of the present study was to determine the systemic levels of oxidative stress markers, such as ischemia-modified albumin (IMA), advanced oxidation protein products (AOPP), ferric reducing antioxidant power (FRAP) and the prooxidant-antioxidant balance (PAB), to clarify protein redox homeostasis in patients with Alzheimer's disease, and to compare them with mentally healthy persons of the same age. METHODS: A total of 38 patients with Alzheimer's disease (AD) and 34 sex- and age-matched mentally healthy control subjects were included in this study. RESULTS: The patients had significantly higher AOPP, IMA and PAB in the patient group than in the control group (P = 0.004, P = 0.001, P = 0.007, respectively). The FRAP was significantly lower in the patients with AD than in the control subjects (P = 0.002), and according to the receiver operating characteristic curves, the IMA and AOPP areas are below the 0.700 receiver operating characteristic curve line (area under the curve 0.817 and 0.730, respectively; 95% CI 0.709-0.898 and 0.612-0.828, respectively). CONCLUSIONS: Increased IMA, AOPP and PAB, and decreased FRAP are likely to be results of oxidative stress, a condition in which an imbalance occurs between the production and inactivation of reactive oxygen species in AD. The IMA could be used for the better evaluation of clinical status, as well as the independent characteristic symptoms of AD, for the purposes of routine clinical laboratory analysis.