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Effect of donepezil and tacrine on oxidative stress in intracerebral streptozotocin-induced model of dementia in mice.
Eur J Pharmacol. 2008 Mar 10; 581(3):283-9.EJ

Abstract

Oxidative stress is a major factor implicated in the degeneration of cholinergic neurons in Alzheimer's disease. Presently, cholinesterase inhibitors are the mainstay of therapy for Alzheimer's disease. However, the potential of cholinesterase inhibitors as antioxidants, an important aspect for neuroprotection, has not been properly investigated. Therefore, the present study was designed to investigate the influence of antidementia drugs, tacrine and donepezil, on biochemical markers of oxidative stress, glutathione (GSH) and malondialdehyde (MDA), and acetylcholinesterase activity in the brain in a streptozotocin-induced experimental model of dementia in mice. Intracerebral (i.c.) injection of streptozotocin at a dose of 0.5 mg/kg on 1st and 3rd days caused significant deficits in memory function, as evaluated in a passive avoidance test and Morris Water Maze (spatial memory) test 14 days after the 1st dose. Mice were treated with tacrine and donepezil at a dose of 5 mg/kg orally in separate groups. Both tacrine- and donepezil-treated mice showed a significant improvement of the streptozotocin (i.c.)-induced memory impairment. Streptozotocin (i.c.) administration caused a significant decrease in GSH and increase in MDA as compared to control, indicating a state of oxidative stress in the brain of streptozotocin (i.c.) amnesic mice. Treatment of streptozotocin (i.c.) amnesic mice with tacrine or donepezil did not cause significant changes in GSH and MDA levels in the brain as compared to control. Streptozotocin amnesic mice had raised acetylcholinesterase activity in the brain while there was a significant decrease in brain acetylcholinesterase activity in tacrine- and donepezil-treated streptozotocin (i.c.) mice. Thus, results indicate that tacrine and donepezil, beside inhibition of acetylcholinesterase, may also suppress oxidative stress.

Authors+Show Affiliations

Division of Pharmacology, Central Drug Research Institute, PO Box 173, Lucknow UP 226001, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18234183

Citation

Saxena, Gunjan, et al. "Effect of Donepezil and Tacrine On Oxidative Stress in Intracerebral Streptozotocin-induced Model of Dementia in Mice." European Journal of Pharmacology, vol. 581, no. 3, 2008, pp. 283-9.
Saxena G, Singh SP, Agrawal R, et al. Effect of donepezil and tacrine on oxidative stress in intracerebral streptozotocin-induced model of dementia in mice. Eur J Pharmacol. 2008;581(3):283-9.
Saxena, G., Singh, S. P., Agrawal, R., & Nath, C. (2008). Effect of donepezil and tacrine on oxidative stress in intracerebral streptozotocin-induced model of dementia in mice. European Journal of Pharmacology, 581(3), 283-9. https://doi.org/10.1016/j.ejphar.2007.12.009
Saxena G, et al. Effect of Donepezil and Tacrine On Oxidative Stress in Intracerebral Streptozotocin-induced Model of Dementia in Mice. Eur J Pharmacol. 2008 Mar 10;581(3):283-9. PubMed PMID: 18234183.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of donepezil and tacrine on oxidative stress in intracerebral streptozotocin-induced model of dementia in mice. AU - Saxena,Gunjan, AU - Singh,Sheelendra Pratap, AU - Agrawal,Rahul, AU - Nath,Chandishwar, Y1 - 2007/12/23/ PY - 2007/07/25/received PY - 2007/11/27/revised PY - 2007/12/13/accepted PY - 2008/2/1/pubmed PY - 2008/5/13/medline PY - 2008/2/1/entrez SP - 283 EP - 9 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 581 IS - 3 N2 - Oxidative stress is a major factor implicated in the degeneration of cholinergic neurons in Alzheimer's disease. Presently, cholinesterase inhibitors are the mainstay of therapy for Alzheimer's disease. However, the potential of cholinesterase inhibitors as antioxidants, an important aspect for neuroprotection, has not been properly investigated. Therefore, the present study was designed to investigate the influence of antidementia drugs, tacrine and donepezil, on biochemical markers of oxidative stress, glutathione (GSH) and malondialdehyde (MDA), and acetylcholinesterase activity in the brain in a streptozotocin-induced experimental model of dementia in mice. Intracerebral (i.c.) injection of streptozotocin at a dose of 0.5 mg/kg on 1st and 3rd days caused significant deficits in memory function, as evaluated in a passive avoidance test and Morris Water Maze (spatial memory) test 14 days after the 1st dose. Mice were treated with tacrine and donepezil at a dose of 5 mg/kg orally in separate groups. Both tacrine- and donepezil-treated mice showed a significant improvement of the streptozotocin (i.c.)-induced memory impairment. Streptozotocin (i.c.) administration caused a significant decrease in GSH and increase in MDA as compared to control, indicating a state of oxidative stress in the brain of streptozotocin (i.c.) amnesic mice. Treatment of streptozotocin (i.c.) amnesic mice with tacrine or donepezil did not cause significant changes in GSH and MDA levels in the brain as compared to control. Streptozotocin amnesic mice had raised acetylcholinesterase activity in the brain while there was a significant decrease in brain acetylcholinesterase activity in tacrine- and donepezil-treated streptozotocin (i.c.) mice. Thus, results indicate that tacrine and donepezil, beside inhibition of acetylcholinesterase, may also suppress oxidative stress. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18234183/Effect_of_donepezil_and_tacrine_on_oxidative_stress_in_intracerebral_streptozotocin_induced_model_of_dementia_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)01327-1 DB - PRIME DP - Unbound Medicine ER -