Beneficial Effects of Donepezil on Vascular Endothelial Dysfunction-Associated Dementia Induced by L-Methionine in Rats

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概要

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• Donepezil (acetyl cholinesterase inhibitor) is a mainstay of clinical intervention to contain memory deficits of Alzheimer's disease. However, its beneficial role in endothelial dysfunction-associated dementia i.e. vascular dementia still needs to be explored. The present study was designed to investigate the effect of donepezil on vascular endothelial dysfunction, and associated memory deficits in rats. Atorvastatin (3-hydroxy-4-methyl-glutaryl (HMG)-CoA inhibitor) was taken as the standard. Rats were administered L-methionine (1.7g/kg per day, p.o., 4 weeks and 4 days i.e. chronic treatment) to produce endothelial dysfunction and dementia. Serum nitrite level was estimated as a marker of endothelial function. Morris water maze (MWM) test was employed for assessment of memory. Brain tissue thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were estimated to assess oxidative stress. Brain acetylcholine esterase (AChE) activity and serum total cholesterol level were also estimated. L-methionine produced endothelial dysfunction as reflected by significant decrease of serum nitrite concentration. L-methionine-treated rats performed poorly on MWM indicating impairment of memory as well. These rats also showed a significant rise in brain oxidative stress, AChE activity and serum total cholesterol levels. Donepezil (0.1mg/kg p.o.) and atorvastatin (10mg/kg p.o.) attenuated L-methionine-induced endothelial dysfunction. This intervention reversed L-methionine-induced rise of brain oxidative stress and AChE activity. Furthermore, atorvastatin produced a reduction of L-methionine-induced rise in serum cholesterol. The beneficial effects of donepezil may be attributed to its multiple effects and this study highlights the potential of donepezil in vascular dementia.

• 2009-04-01

著者

• Singh Nirmal

  Pharmacology Division Department Of Pharmaceutical Sciences And Drug Research Punjabi University

• Jaggi Amteshwar

  Pharmacology Division Department Of Pharmaceutical Sciences And Drug Research Punjabi University

• Sharma Bhupesh

  Pharmacology Division Department Of Pharmaceutical Sciences And Drug Research Punjabi University

• Koladiya Rajeshkumar

  Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Punjabi University

• Koladiya Rajeshkumar

  Pharmacology Division Department Of Pharmaceutical Sciences And Drug Research Punjabi University

• Singh Nirmal

  Pharmacology Division Department Of Pharmaceutical Sciences & Drug Research Punjabi University

関連論文

• Beneficial Effects of Donepezil on Vascular Endothelial Dysfunction-Associated Dementia Induced by L-Methionine in Rats
• Reversal of Memory Deficits by Atorvastatin and Simvastatin in Rats
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