title: CuO nanoparticles induce apoptosis by impairing the antioxidant defense and detoxification systems in the mouse hippocampal HT22 cell line: protective effect of crocetin.
abstract: Several studies have reported that CuO nanoparticles (CuONPs) have the capacity to cross the blood brain barrier and exert a toxic effect. The aims of our study were to investigate mechanisms underlying CuONPs-induced neurotoxicity in vitro and neuroprotective effects of crocetin. We investigated the toxicological effects of exposure of HT22 hippocampal cells to CuONPs (31 nm) in the presence or absence of crocetin. Crocetin is a carotenoid with wide spectrum of pharmacological effects and the ability to cross blood-brain barrier. Exposure of HT22 cells to CuONPs resulted in: (1) increased cell death in a time- and concentration-dependent manner, with a LC50 of 25.9 μg/ml after 24 h; (2) decreased antioxidant/detoxification enzymes activities: glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione S-tranferase (GST), and reduced glutathione (GSH) levels; (3) decreased gene expression of GPx and SOD; (4) reactive oxygen species (ROS) generation; (5) enhanced apoptosis; and (6) up-regulation of the pro-apoptotic genes Bax, and down-regulation of anti-apoptotic genes Bcl-2. Importantly, all these effects were significantly attenuated by co-incubation of hippocampal cells with 5 μM crocetin.
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Niska
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, The University of Dublin Trinity College, Dublin, Ireland.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Santos-Martinez
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, The University of Dublin Trinity College, Dublin, Ireland; Kardio-Med Silesia, Zabrze, Poland.
authors.forename: Marek Witold
authors.initials: MW
authors.lastname: Radomski
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, Poland. Electronic address: iinkiel@gumed.edu.pl.
authors.forename: Iwona
authors.initials: I
authors.lastname: Inkielewicz-Stepniak
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002338:Carotenoids / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008027:Light; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D012542:Scattering, Radiation; D013482:Superoxide Dismutase / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D003300:Copper; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; C030973:cupric oxide
keywords: Antioxidant/detoxification system; Apoptosis; Crocetin; CuO nanoparticles; Mouse hippocampal cell line; Reactive oxygen species