Effects of L-Serine Against Cisplatin-Mediated Reactive Oxygen Species Generation in Zebrafish Vestibular Tissue Culture and HEI-OC1 Auditory Hybridoma Cells

Neurotox Res. 2021 Feb;39(1):36-41. doi: 10.1007/s12640-020-00188-y. Epub 2020 Mar 27.

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.

Keywords: Cisplatin; HEI-OC1 cells; L-serine; Ototoxicity; Reactive oxygen species; Zebrafish tissue culture.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cisplatin / toxicity*
  • Female
  • Hybridomas / drug effects*
  • Hybridomas / metabolism*
  • Male
  • Reactive Oxygen Species / metabolism*
  • Saccule and Utricle / drug effects*
  • Saccule and Utricle / metabolism*
  • Serine / administration & dosage*
  • Tissue Culture Techniques
  • Zebrafish

Substances

  • Reactive Oxygen Species
  • Serine
  • Cisplatin