Zebrafish embryos as an in vivo model to investigate cisplatin-induced oxidative stress and apoptosis in mitochondrion-rich ionocytes

Abstract

Pharmaceuticals and personal care products are emerging environmental pollutants. Cisplatin, one of the most widely used platinum-based chemotherapeutic agents, has been found to contaminate aquatic environments. Using zebrafish embryos as a model, cisplatin was previously found to impair skin ionocytes and ion regulation. The purpose of this study was to further investigate how cisplatin damages ionocytes. Zebrafish embryos were exposed to cisplatin (0, 50, and 100 μM) for 96 h (4-100 h post-fertilization) and then stained with fluorescent dyes to reveal mitochondrial activity (rhodamine123), apoptosis (acridine orange), and oxidative stress (CellROX/MitoSOX) in ionocytes of living embryos. Results showed that cisplatin exposure decreased rhodamine 123-labeled ionocytes, induced oxidative stress in ionocytes, and promoted apoptosis in a concentration-dependent manner. Quantitative PCR analysis showed that mRNA levels of antioxidative genes (sod1, sod2, gpx1a, and cat) and an apoptotic gene (caps3a) were induced. In the time-course experiment at 96-98 h post-fertilization, cisplatin increased oxidative stress and apoptosis in ionocytes in a time-dependent manner. In conclusion, this study demonstrates that cisplatin exposure induces oxidative stress, mitochondrial damage, and apoptosis in ionocytes of zebrafish embryos.

Keywords: Apoptosis; Cisplatin; Ionocyte; Mitochondria damage; Nephrotoxicity; Oxidative stress; Zebrafish.