title: Tempol and perindopril protect against lipopolysaccharide-induced cognition impairment and amyloidogenesis by modulating brain-derived neurotropic factor, neuroinflammation and oxido-nitrosative stress.
abstract: We aim to evaluate the protective role of the central angiotensin-converting enzyme (ACE) inhibitor perindopril, compared with the standard reactive oxygen species (ROS) scavenger tempol, against lipopolysaccharide (LPS)-induced cognition impairment and amyloidogenesis in a simulation to Alzheimer's disease (AD). Mice were allocated into a control group, an LPS control group (0.8 mg/kg, i.p., once), a tempol (100 mg/kg/day, p.o., 7 days) treatment group, and two perindopril (0.5 and 1 mg/kg/day, p.o., 7 days) treatment groups. A behavioral study was conducted to evaluate spatial and nonspatial memory in mice, followed by a biochemical study involving assessment of brain levels of Aβ and BDNF as Alzheimer and neuroplasticity markers; tumor necrosis factor-alpha (TNF-α), nitric oxide end-products (NOx), neuronal nitric oxide synthase (nNOS), and inducible nitric oxide synthase (iNOS) as inflammatory markers; and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH), and nitrotyrosine (NT) as oxido-nitrosative stress markers. Finally, histopathological examination of cerebral cortex, hippocampus, and cerebellum sections was performed using both routine and special staining. Tempol and perindopril improved spatial and nonspatial memory in mice without affecting locomotor activity; decreased brain Aβ deposition and BDNF depletion; decreased brain TNF-α, NOx, nNOS, iNOS, MDA, and NT levels; and increased brain SOD and GSH contents, parallel to confirmatory histopathological findings. Tempol and perindopril may be promising agents against AD progression via suppression of Aβ deposition and BDNF decline, suppression of TNF-α production, support of brain antioxidant status, and amelioration of oxido-nitrosative stress and NT production.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Beni Suef Governorate, Egypt.
authors.forename: Mohammed Ragab Abdel-Aziz
authors.initials: MR
authors.lastname: Ali
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Beni Suef Governorate, Egypt.
authors.forename: Amira Morad Hussein
authors.initials: AM
authors.lastname: Abo-Youssef
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Beni Suef Governorate, Egypt. drbasimanwar2006@yahoo.com.
authors.forename: Basim Anwar Shehata
authors.initials: BA
authors.lastname: Messiha
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo University Rd, Oula, Giza Governorate, Egypt.
authors.forename: Mahmoud Mohamed
authors.initials: MM
authors.lastname: Khattab
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D020913:Perindopril / Q000494:pharmacology*; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects; D013113:Spin Labels; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D003497:Cyclic N-Oxides; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D026361:Reactive Nitrogen Species; D013113:Spin Labels; C001803:tempol; D020913:Perindopril
keywords: Amyloidogenesis; Brain-derived neurotropic factor; Neuroinflammation; Oxido-nitrosative stress; Perindopril; Tempol