الفهرس 
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Abstract
Cyclophosphamide (CP) is a powerful chemotherapeutic drug that causes neurodegenerative diseases and cognitive impairment due to the overproduction of reactive oxygen species (ROS). Quercetin (Qu) is a potent flavanol antioxidant that is a member of the flavonoid family and is naturally present in plants. Qu contains a wide range of biological activities, including its ability to act as a neuroprotective, anti-cancer, anti-diabetic, anti-inflammatory, and radical scavenger. This study was conducted to assess the protective role of Qu and Qu-Ch NPs against the oxidative insults and harmful effects caused by CP on the rat brain. For this aim, thirty-six male albino rats were randomly classified into six groups (n=6). CP (75 mg/kg bwt) was administered intraperitoneally at a single dose 24 hours before the termination of the experiment; Rats were pretreated with Qu and Qu-Ch NPs orally in doses of 10 mg/kg bwt daily for 2 weeks. At the end of the experimental period, all animals were sacrificed, and blood samples and brain were collected for different analyses. Results revealed that CP causes neurobehavioral alterations and impaired brain neurochemical status, as shown by a significant decrease in brain glutathione (GSH), serum total antioxidant capacity (TAC), and serotonin (5-HT) levels, while concentrations of malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor (TNF), and choline esterase (ChE) increased significantly in comparison to the control group. Through modulating those parameters, pretreatment with Qu and Qu-Ch NPs showed a strong anti-oxidative, anti-depressive, and neuroprotective effect. In order to identify the precise brain-altered regions, histological studies were carried out together with the expression levels of some chosen genes in brain homogenates to further validate the findings. Results of gene expression analysis showed up regulation of Nrf2, HO-1, NF-κB, and Cox-2, while, Keap1 expression levels were down-regulated in brain homogenates of CP exposed group in comparison with control group as well as Qu and Qu-Ch NPs pretreatment groups. It could be concluded that Qu and Qu-Ch NPs pretreatment can protect against CP-induced neurotoxicity owing to its anti-lipid per oxidation, anti-oxidant and anti-apoptotic properties.