ABSTRACT
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.
Subject(s)
Dendrimers/toxicity , Viologens/toxicity , Animals , Apoptosis/drug effects , Catalase/metabolism , Cell Cycle Checkpoints , Cell Line , Cell Shape/drug effects , Cell Survival/drug effects , Drug Evaluation, Preclinical , Glutathione/metabolism , Hippocampus/cytology , Membrane Potential, Mitochondrial/drug effects , Mice , Neurons/drug effects , Neurons/physiology , Organophosphonates/toxicity , Reactive Oxygen Species/metabolismABSTRACT
Alkyl viologens showed cytotoxicity when incubated with cultured murine leukemia L1210 cells for 48 h, whereas they were not cytotoxic when briefly incubated for 10 min. Under the permeabilizing conditions achieved by vortex-stirring with a high molecular weight polyacrylic acid (A-119), appreciable cytotoxicity was shown even after a 10-min exposure to any of the alkyl and amino viologens examined. Acetylamino viologen showed no cytotoxicity regardless of the presence or absence of A-119. This permeabilizing procedure was demonstrated to be applicable to internalize water-soluble positively charged viologen molecules into the cell.
Subject(s)
Acrylic Resins/chemistry , Herbicides/toxicity , Leukemia L1210/pathology , Viologens/toxicity , Animals , Cell Survival/drug effects , Mice , Molecular Weight , Tumor Cells, CulturedABSTRACT
Methyl (paraquat), propyl, isopropyl, butyl, methyl-pentyl, hexyl, octyl and benzyl viologens (1,1'-Alkyl-4,4'-bipyridylium salts) were administered subcutaneously to female Sprague-Dawley rats to determine relative toxicities. These compounds all produce the spectrum of effects previously reported for paraquat and additionally produce a focal necrosis at the injection site, nonemptying of the stomach and adrenal enlargement. A lethal dose of propyl, hexyl or benzyl viologen often produced a yellow to red serous fluid in the pleural cavity. Many of the signs observed with viologen poisoning are similar to adrenal hormone effects and the suggestion is made that the adrenals may be contributing to toxicity.
