CuO nanoparticles induce apoptosis by impairing the antioxidant defense and detoxification systems in the mouse hippocampal HT22 cell line: Protective effect of crocetin

- Neurotoxicity of CuO nanoparticles was investigated in mouse hippocampal cells.
- CuONPs caused dysregulation of apoptosis genes and induced programmed cell death.
- This was associated with dysregulation of the antioxidant/detoxification systems.
- The carotenoid, crocetin, protected cells from CuONPs-induced neurotoxicity.

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.