Promising low-toxicity of viologen-phosphorus dendrimers against embryonic mouse hippocampal cells

• Published in: Molecules (Basel, Switzerland) Vol. 18; no. 10; pp. 12222 - 12240
• Main Authors: Lazniewska, Joanna, Janaszewska, Anna, Miłowska, Katarzyna, Caminade, Anne-Marie, Mignani, Serge, Katir, Nadia, El Kadib, Abdelkrim, Bryszewska, Maria, Majoral, Jean-Pierre, Gabryelak, Teresa, Klajnert-Maculewicz, Barbara
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.09.2013; MDPI
• Subjects: Alzheimer's disease; Animals; Apoptosis; Apoptosis - drug effects; Catalase - metabolism; Cell cycle; Cell Cycle Checkpoints; Cell Line; Cell Shape - drug effects; Cell Survival - drug effects; Cytotoxicity; Dendrimers - toxicity; Disease; Drug Evaluation, Preclinical; Glutathione - metabolism; hippocampal cell line; Hippocampus - cytology; Membrane Potential, Mitochondrial - drug effects; Mice; Neuroblastoma; Neurons - drug effects; Neurons - physiology; Organophosphonates - toxicity; Parkinson's disease; Phosphorus; Reactive Oxygen Species - metabolism; ROS; Toxicity; viologen-phosphorus dendrimers; Viologens - toxicity; France
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules181012222

A new class of viologen-phosphorus dendrimers (VPDs) has been recently shown to possess the ability to inhibit neurodegenerative processes in vitro. Nevertheless, in the Central Nervous Systems domain, there is little information on their impact on cell functions, especially on neuronal cells. In this work, we examined the influence of two VPD (VPD1 and VPD3) of zero generation (G0) on murine hippocampal cell line (named mHippoE-18). Extended analyses of cell responses to these nanomolecules comprised cytotoxicity test, reactive oxygen species (ROS) generation studies, mitochondrial membrane potential (ΔΨm) assay, cell death detection, cell morphology assessment, cell cycle studies, as well as measurements of catalase (CAT) activity and glutathione (GSH) level. The results indicate that VPD1 is more toxic than VPD3. However, these two tested dendrimers did not cause a strong cellular response, and induced a low level of apoptosis. Interestingly, VPD1 and VPD3 treatment led to a small decline in ROS level compared to untreated cells, which correlated with slightly increased catalase activity. This result indicates that the VPDs can indirectly lower the level of ROS in cells. Summarising, low-cytotoxicity on mHippoE-18 cells together with their ability to quench ROS, make the VPDs very promising nanodevices for future applications in the biomedical field as nanocarriers and/or drugs per se.