title: Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation, and amyloidogenesis: possible role of brain-derived neurotrophic factor.
abstract: Angiotensin II has pro-inflammatory and pro-oxidant potentials. We investigated the possible protective effects of the Angiotensin II receptor blocker telmisartan, compared with the superoxide scavenger tempol, on lipopolysaccharide (LPS)-induced cognitive decline and amyloidogenesis. Briefly, mice were allocated into a normal control group, an LPS control group, a tempol treatment group, and 2 telmisartan treatment groups. A behavioral study was conducted followed by a biochemical study via assessment of brain levels of beta amyloid (Aβ) and brain-derived neurotropic factor (BDNF) as amyloidogenesis and neuroplasticity markers, tumor necrosis factor alpha (TNF-α), nitric oxide end products (NOx), neuronal and inducible nitric oxide synthase (nNOS and 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 routine and special Congo red stains. Tempol and telmisartan improved cognition, decreased brain Aβ deposition and BDNF depletion, decreased TNF-α, NOx, nNOS, iNOS, MDA, and NT brain levels, and increased brain SOD and GSH contents, parallel to confirmatory histopathological evidences. In conclusion, tempol and telmisartan are promising drugs in managing cognitive impairment and amyloidogenesis, at least via upregulation of BDNF with inhibition of neuroinflammation and oxido-nitrosative stress.
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Egypt.
authors.forename: Waleed A I
authors.initials: WAI
authors.lastname: Khallaf
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Egypt.
authors.forename: Basim A S
authors.initials: BAS
authors.lastname: Messiha
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Egypt.
authors.forename: Amira M H
authors.initials: AMH
authors.lastname: Abo-Youssef
authors.affiliation: b Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza, Egypt.
authors.forename: Nesrine S
authors.initials: NS
authors.lastname: El-Sayed
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000139:chemically induced / Q000188:drug therapy*; D003497:Cyclic N-Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D019610:Cytoprotection / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D013113:Spin Labels; D000077333:Telmisartan
chemical_list: D000682:Amyloid; D001562:Benzimidazoles; D001565:Benzoates; D019208:Brain-Derived Neurotrophic Factor; D003497:Cyclic N-Oxides; D008070:Lipopolysaccharides; D013113:Spin Labels; D000077333:Telmisartan; C001803:tempol
keywords: amyloidogenesis; amyloïdogenèse; brain-derived neurotropic factor; facteur neurotrophique dérivé du cerveau; neuro-inflammation; neuroinflammation; telmisartan; tempol