TY - BOOK AU - Abulfadl,Yasmin Saad AU - Ahmed,Amany AIi Eissa AU - Badary,Osama Ahmed AU - EI-Maraghy,Nabila Nour Eldin TI - Effects of Thymoquinone on Behavioral and Biological Alterations in an Experimental Rat Model of Alzheimer Disease U1 - 615.19 22 PY - 2018///] KW - Drug development KW - Abbreviations KW - Acronyms KW - Pharmaceutical industry KW - Drug Design KW - Handbooks KW - Drug Industry KW - Pharmaceutical Preparations N1 - Thesis (PH.D.)- Ain Shams University. Faculty of Pharmacy. Pharmaceutical Chemistry Department,2018; Includes bibliographic references (p. 194 - 241) N2 - neuroprotective effect of thymoquinone (TQ) on Alzheimer disease (AD) pathogenesis by comparing the effect of three different doses of(TQ) (10, 20,.40mg/kg) on AD rat model and on normal animals. The study was further extended to illuminate the mechanistic pathways influenced by TQ treatment. AD experimental model was established in Sprague Dawley male albino rats by intraperitoneal injection of both D-galactose (D-gal) (60mg/kg) and aluminum chloride (AICI3) (lOmg/kg) for 42 days. After injection of D-gal and AICl3 for 28 days, the rats were treated concomitantly with PO administration of TQ at 10, 20, 40 mg/kg/day doses levels once daily for consecutive 14 days respectively. Behavioral responses of animals were assessed in a Morris water maze and passive avoidance tests. At the end of this period all rats were anaesthetized and sacrificed by cervical dislocation. Brains were carefully excised and divided sagittally. The left hemibrains were immediately fixed in 4% PF A for histology and immunohistochemistry. The right hemibrains were homogenized for analyzing of biochemical changes by assessing oxidative stress biomarkers such as nitric oxide (NO) and malondialdehyde (MDA), anti-oxidant biomarkers such as total antioxidant capacity (T AC) and superoxide dismutase, antiapoptotic biomarker such as beta cel1 lymphoma-2 (Bcl-2), the specific proinflammatory cytokines such as tumor necrosis factor (TNF-a.) and interleukin- 1 beta (lL-l~) and brain cholinergic biomarkers, such as acetylcholinesterase (AChE) as well as assessment of brain derived neurotrophic factor (BDNF). Then the study was further extended to investigate the mechanistic pathways influenced by TQ treatment by studying and understanding the key signal ER -