Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10137703 | Chemico-Biological Interactions | 2018 | 46 Pages |
Abstract
The present study evaluated the neuroprotective effects of one selenium-containing AZT derivative compound (S1073) in memory and learning impairment caused by Intracerebroventricular-streptozotocin (ICV-STZ). ICV-STZ in mice causes impairment of energy metabolism with oxidative damage and cholinergic dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's type (AD). Acetylcolinesterase (AChE), Catalase (CAT), dichlorofluorescein oxidation (DCFH), TBARS and thiol content were measured. Swiss adult mice were pre-treated with S1073 [1â¯mmol/kg] (i.p.) and after 30â¯min of the injection received a bilateral dose of STZ [11.3â¯Î¼mol/l]. After 8 days' STZ injection, we performed the behavioral experiments (Beaker test, Open field and Morris water maze task). ICV-STZ caused significant learning and memory impairments, which were significantly improved by S1073 pre-treatment. A significant increase in cerebral DFCH, TBARS levels and AChE activity and a disturbance in the memory and learning were observed in ICV-STZ injected animals. S1073 significantly ameliorated all alterations induced by ICV-STZ in mice. All these findings support the neuroprotective role of S1073 in mice model of Alzheimer's dementia-type induced by ICV-STZ, which may be associated with its antioxidant activity and/or with its inhibitory effect in brain AChE. In fact, in silico analysis indicated that S1073 may be an inhibitor of AChE.
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Authors
Gustavo Roberto Thomé, Vitor Antunes Oliveira, Maria Rosa Chitolina Schetinger, Rogério Aquino Saraiva, Diego Souza, Oscar Endrigo Dorneles Rodrigues, João Batista Teixeira Rocha, Rafael Porto Ineu, Maria Ester Pereira,