An In Vitro Assessment Method for Chemotherapy-Induced Peripheral Neurotoxicity Caused by Anti-Cancer Drugs Based on Electrical Measurement of Impedance Value and Spontaneous Activity.

ABSTRACT

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major adverse event of anti-cancer drugs, which still lack standardized measurement and treatment methods. In the present study, we attempted to evaluate neuronal dysfunctions in cultured rodent primary peripheral neurons using a microelectrode array system. After exposure to typical anti-cancer drugs (i.e., paclitaxel, vincristine, oxaliplatin, and bortezomib), we successfully detected neurotoxicity in dorsal root ganglia neurons by measuring electrical activities, including impedance value and spontaneous activity. The impedance value decreased significantly for all compounds, even at low concentrations, which indicated cell loss and/or neurite degeneration. The spontaneous activity was also suppressed after exposure, which suggested neurotoxicity again. However, an acute response was observed for paclitaxel and bortezomib before toxicity, which showed different mechanisms based on compounds. Therefore, MEA measurement of impedance value could provide a simple assessment method for CIPN, combined with neuronal morphological changes.