Abstract
Cisplatin is a platinum-based chemotherapy compound effective against a variety of cancers. However, it can cause increased reactive oxygen species (ROS) production in auditory and vestibular tissue leading to permanent hearing and balance loss. The amino acid, L-serine, has been shown to reduce ROS in some tissue types. In this project, we first investigated whether L-serine could reduce cisplatin-mediated ROS generation in zebrafish utricular tissue culture using spectrophotometry and the fluorescent ROS detector dye, H2DCFDA. Then, we examined whether L-serine could prevent the effect of cisplatin against cellular viability in the mouse auditory hybridoma cell line, HEI-OC1, using the spectrophotometric (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. As a final step, we used H2DCFDA dye and flow cytometry analysis to determine if L-serine could counteract the effect of cisplatin on ROS production in this cell line. We found that cisplatin and L-serine treatment may influence ROS production in utricular tissue. Further, although L-serine did not counteract the effect of cisplatin against HEI-OC1 cellular viability, the amino acid did prevent the platinum compound’s effect to increase ROS in these cells. These results suggest that L-serine may act in auditory and vestibular tissues as an effective protectant against cisplatin-mediated toxicity.
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Acknowledgment
We thank Dr. Paul A. Cox for the L-serine that was used in our initial experiments.
Funding
This project was funded by the National Institutes of Health awards T1 R15 CA188890-01A1 and 2 P20 GM103436-19 to M.E.S. and through the Western Kentucky University Gatton Academy of Mathematics and Science Summer Research Internship Grant to both Elvin Irihamye and Satya Moolani.
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Monroe, J.D., Moolani, S.A., Irihamye, E.N. et al. Effects of L-Serine Against Cisplatin-Mediated Reactive Oxygen Species Generation in Zebrafish Vestibular Tissue Culture and HEI-OC1 Auditory Hybridoma Cells. Neurotox Res 39, 36–41 (2021). https://doi.org/10.1007/s12640-020-00188-y
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DOI: https://doi.org/10.1007/s12640-020-00188-y