title: Trimetazidine prevents oxidative changes induced in a rat model of sporadic type of Alzheimer's disease.
abstract: Oxidative stress plays a major role in the pathogenesis of Alzheimer's disease (AD) of sporadic origin. The expression of DHCR24 (Seladin-1), marker for neuronal oxidative stress and degeneration, has been reported to be altered in the brains of AD patients. In the present study, we investigated the effect of trimetazidine (TMZ) on the hippocampal oxidative parameters and the expression of DHCR24 (Seladin-1) in an animal model of sporadic AD. Male rats were pre-treated with TMZ (25 mg/kg) after which injected with intracerebroventricular-streptozotocin (ICV-STZ)/Saline. Following 2, 7 and 14 days, animals of different groups were sacrificed with their brain excised to detect the hippocampal lipid peroxidation, superoxide dismutase (SOD), catalase activity, DHCR24 (Seladin-1) expression and possible histopathological changes. ICV-STZ administration induced significant oxidative changes in the hippocampus. Meanwhile, TMZ pre-treatment showed to ameliorate the oxidative stress, which was demonstrated by a significant rise in the hippocampal SOD and catalase activity, as well as a significant decrease in the malondialdehyde (MDA) level. TMZ administration also increased the expression of DHCR24 (Seladin-1) gene in the hippocampus. In conclusion, our findings indicated a neuroprotective effect of TMZ possibly related to its antioxidant activity resulting in the up-regulation of DHCR24 (Seladin-1). Such TMZ effects may be beneficial in minimizing oxidative stress in sporadic Alzheimer's disease and possible prevention of disease progression.
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. zahmatkm@tums.ac.ir.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Hassanzadeh
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. zahmatkm@tums.ac.ir.
authors.forename: Amir
authors.initials: A
authors.lastname: Hosseini
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. zahmatkm@tums.ac.ir.
authors.forename: Parichehr
authors.initials: P
authors.lastname: Pasbakhsh
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. zahmatkm@tums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Akbari
authors.affiliation: Iranian Research Organizations for Science and Technology (IROST), Tehran, Iran. zahmatkm@tums.ac.ir.
authors.forename: Massoud
authors.initials: M
authors.lastname: Ghaffarpour
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. zahmatkm@tums.ac.ir.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Takzare
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. zahmatkm@tums.ac.ir.
authors.forename: Maryam
authors.initials: M
authors.lastname: Zahmatkesh
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014292:Trimetazidine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D009419:Nerve Tissue Proteins; D014665:Vasodilator Agents; D013482:Superoxide Dismutase; D014292:Trimetazidine