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Updated: Jun 9, 2026
Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
Published on: April 26, 2012
Evaluation of nerve cell toxicity in vitro by electrophysiological and biochemical methods
1Institute of Toxicology, Department of Public Health, Shandong Medical University, Jinan 250012, P.R. China.
Abstract:
The acute toxicity of the first nine standard chemicals in the Multicentre Evaluation of In Vitro Cytotoxicity Tests (MEIC) programme was evaluated in the NG108-15 neuroblastoma cell line by monitoring changes in cell resting membrane potential (RMP) and by using the MTT assay to measure cell viability. Cells were differentiated with dibutyryl-cAMP and then exposed to different concentrations of the chemicals for 1 hr or 24 hr. At each concentration and time point, RMPs were measured from about 30 differentiated cells and MTT assays were performed on parallel cultures. IC(50) values were obtained from linear regression analysis. The results showed that the IC(50)s from MTT assays correlated closely with those from RMP measurements (r = 0.983 for 1 hr exposure; r = 0.933 for 24 hr exposure). IC(50)s of amitriptyline and diazepam were 0.1-1.9 mm; alcoholic compounds (isopropanol, ethylene glycol, ethanol and methanol) had IC(50)s from 121.5 mm to 3731.9 mm; paracetamol, aspirin and ferrous sulphate had intermediate cytotoxicity (IC(50) 2.6-53.5 mm). IC(50)s decreased markedly with increased exposure time. RMP is expected to be a sensitive indicator of the health of nerve cells; however, its measurement in a large number of cells is laborious. MTT assays are rapid, and the close correlation between IC(50)s in the two types of assay suggests that MTT assays could be used to evaluate cytotoxicity in neuronal cells in vitro.
Insights
The MTT assay effectively measures chemical toxicity in neuronal cells, closely correlating with resting membrane potential changes. This rapid method aids in evaluating cytotoxicity in vitro.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- The Multicentre Evaluation of In Vitro Cytotoxicity Tests (MEIC) program aims to standardize cytotoxicity testing.
- Neuronal cell lines like NG108-15 are crucial models for studying neurotoxicity.
- Assessing chemical impact on cell viability and function is vital in toxicology.
Purpose of the Study:
- To evaluate the acute toxicity of nine standard chemicals using the NG108-15 neuroblastoma cell line.
- To compare the efficacy of measuring changes in cell resting membrane potential (RMP) versus the MTT assay for cytotoxicity assessment.
- To determine the correlation between RMP measurements and MTT assay results in response to chemical exposure.
Main Methods:
- NG108-15 neuroblastoma cells were differentiated and exposed to varying concentrations of nine MEIC chemicals for 1 or 24 hours.
- Cell resting membrane potential (RMP) was measured in differentiated cells.
- Cell viability was assessed using the MTT assay on parallel cultures.
- Half maximal inhibitory concentration (IC50) values were calculated via linear regression analysis.
Main Results:
- A strong positive correlation was observed between IC50 values derived from MTT assays and RMP measurements (r=0.983 for 1 hr, r=0.933 for 24 hr).
- Chemicals exhibited a range of toxicities: amitriptyline and diazepam (0.1-1.9 mM), paracetamol, aspirin, and ferrous sulfate (2.6-53.5 mM), and alcohols like isopropanol and ethanol (121.5-3731.9 mM).
- Cytotoxicity, indicated by lower IC50 values, increased significantly with longer exposure times.
Conclusions:
- The MTT assay provides a reliable and rapid method for evaluating chemical cytotoxicity in neuronal cells.
- MTT assay results closely mirror changes in resting membrane potential, a sensitive indicator of neuronal health.
- The findings support the use of MTT assays as a practical alternative to laborious RMP measurements for in vitro neurotoxicity screening.
