Acute in vitro neurotoxicity of some pyrethroids using microelectrode arrays

• Published in: Toxicology in vitro 2018-03, Vol.47, p.165-177
• Main Authors: Baskar, Mohana Krishnan, Murthy, Prakhya Balakrishna
• Format: Article
• Language: English
• Subjects: Acute in vitro neurotoxicity; Animals; Cell Size - drug effects; Cell Survival - drug effects; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cyhalothrin; Cypermethrin; Deltamethrin; Electrodes; Evoked Potentials - drug effects; Excitability; Fetus - cytology; Firing rate; Hormesis - drug effects; Insecticides; Insecticides - toxicity; Lab-On-A-Chip Devices; Mathematical analysis; Microarray Analysis; Microelectrode array; Microelectrodes; Microscopy, Fluorescence; Neural networks; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neurotoxicity; Osmolar Concentration; Parameters; Permethrin; Pyrethrins - toxicity; Pyrethroids; Rats, Wistar; Reproducibility of Results; Statistical analysis; Synaptic Transmission - drug effects; Toxicity Tests, Acute
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2017.11.010

Pyrethroid-mediated changes on microelectrode array (MEA) parameters, such as mean firing rate (MFR), mean burst rate (MBR), and number of active channels (nAC) were investigated by exposing neuronal networks to cumulative concentrations (0.01, 0.1, 1, 10, and 100μM) of pyrethroids (Type-1, bifenthrin and permethrin; Type-2, beta-cyfluthrin, cypermethrin, deltamethrin, and lambda-cyhalothrin). The average MFR, MBR, and nAC increased for all pyrethroids (except nAC for deltamethrin) at lower concentrations and decreased at higher concentrations. The increase in the average MFR, MBR, and nAC was not statistically significant in most of the cases. Increase in MFR, MBR, and nAC was observed in 19/19, 18/19, and 12/19 individual experiments, respectively, at lower concentrations. The IC50s calculated on MEA parameters were more or less similar. The relative potencies calculated on the IC50s of MEA parameters had a strong positive correlation. These observations indicate that the MEA parameters MFR, MBR, and nAC follow the same trend for pyrethroid-mediated changes, and provide a similar outcome. The rank orders of relative potencies on the IC50s of the MEA parameters distinguish type-1 pyrethroids from type-2 pyrethroids, with type-2 being more potent. As increase in MFR at the lower concentrations of pyrethroids was observed in all the individual experiments (19/19), it may be considered as the characteristic effect of pyrethroids on neuronal excitability. •Pyrethroids raise neuronal firing rate (FR) and burst rate (BR) at lower concentrations.•Pyrethroids raise number of active channels (nAC) in MEA chip at lower concentrations.•Pyrethroids inhibit FR, BR, and nAC at higher concentrations.•The IC50s of FR, BR, and nAC were more or less similar among each other.•Type-2 pyrethroids were more potent than type-1 pyrethroids.