A Purine Derivative Containing an Organoselenium Group Protects Against Memory Impairment, Sensitivity to Nociception, Oxidative Damage, and Neuroinflammation in a Mouse Model of Alzheimer's Disease.

In the present study, the effect of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) was tested against memory impairment and sensitivity to nociception induced by intracerebroventricular injection of amyloid-beta peptide (Aß) (25-35 fragment), 3 nmol/3 µl/per site in mice. Memory impairment was determined by the object recognition task (ORT) and nociception by the Von-Frey test (VFT). Aß caused neuroinflammation with upregulation of glial fibrillary acidic protein (GFAP) (in hippocampus), nuclear factor-κB (NF-κB), and the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in cerebral cortex and hippocampus. Additionally, Aß increased oxidant levels and lipid peroxidation in cerebral cortex and hippocampus, but decreased heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prdx1) expression in the hippocampus. Anti-neuroinflammatory effects of FSP were demonstrated by a decrease in the expression of GFAP and NF-κB in the hippocampus, as well as a decrease in proinflammatory cytokines in both the hippocampus and cerebral cortex FSP protected against oxidative stress by decreasing oxidant levels and lipid peroxidation and by increasing HO-1 and Prdx1 expressions in the hippocampus of mice. Moreover, FSP prevented the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2) in the hippocampus of mice induced by Aß. In conclusion, treatment with FSP attenuated memory impairment, nociception sensitivity by decreasing oxidative stress, and neuroinflammation in a mouse model of Alzheimer's disease.

QCTA-1, a quinoline derivative, ameliorates pentylenetetrazole-induced kindling and memory comorbidity in mice: Involvement of antioxidant system of brain.

The present study evaluated the protective effect of 1-(7-chloroquinolin-4-yl)-5-methyl-N-phenyl-1H-1,2,3-triazole-4-carboxamide (QTCA-1) on seizure severity, oxidative stress, and memory disorder in a pentylenetetrazole (PTZ)-kindling model in mice. Male Swiss mice were treated with QTCA-1 (10 mg/kg, intragastrically (i.g.)) or phenobarbital (PHEN) (10 mg/kg; i.g.), 30 min before the injection of PTZ (35 mg/kg, intraperitoneally (i.p.)). Treatments with QCTA-1 or PHEN and PTZ were performed once every 48 h (on the 1st, 3rd, 5th, 7th, 9th and 11th days). After each PTZ injection, the animals were observed for 30 min to assess the stage of seizure intensity. Behavioral parameters were evaluated from the 12th day until the 16th day of the experimental protocol. On the 16th day, mice were euthanized, and the cerebral cortex and hippocampus of mice were removed to determine the thiobarbituric acid reactive species (TBARS) and reactive species (RS) levels, and superoxide dismutase (SOD), Na+/K+-ATPase and acetylcholinesterase (AChE) activities. Our results demonstrated that QTCA-1 significantly decreased the seizure stage score in PTZ-kindled mice. QCTA-1 protected against memory impairment induced by PTZ. QTCA-1 normalized oxidative stress and Na+/K+-ATPase activity in the cerebral structures of PTZ-kindled mice. The effect of QTCA-1 treatment was similar to the positive control used in this study (PHEN). AChE activity did not change in the cerebral structures in PTZ- kindling mice. In conclusion, QCTA-1 may be a promising tool for the treatment of epileptogenesis and epilepsy-associated comorbidity (memory impairment). QCTA-1 to prevent these alterations may involve the reduction of oxidative stress and normalization of Na+/K+-ATPase activity.