TY - JOUR
T1 - Cisplatin exposure impairs ionocytes and hair cells in the skin of zebrafish embryos
AU - Hung, Giun Yi
AU - Wu, Ciao Ling
AU - Chou, Yi Ling
AU - Chien, Chiang Ting
AU - Horng, Jiun Lin
AU - Lin, Li Yih
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/4
Y1 - 2019/4
N2 - This study aimed to assess the sublethal effects of a platinum-based compound, cisplatin, using a zebrafish model. Zebrafish embryos were incubated in different concentrations of cisplatin at 0–96 h post-fertilization. Using a non-invasive, scanning ion-selective electrode technique (SIET), we measured the functions of hair cells (Ca2+ influx) and ionocytes ([H+] gradients). The survival rate, hatching rate, phenotype, body length, whole-body ion (Na+, Cl−, and Ca2+) and Pt contents were also determined. The effects of cisplatin on zebrafish embryos were demonstrated as first impairing hair cell function (at 1 μM of cisplatin), the hair cell number, and body ion content of Cl− (at 10 μM of cisplatin), then decreasing ionocyte acid secretion and overall body ion contents of Na+ and Ca2+ (at 50 μM of cisplatin). The body length and ionocyte density decreased at 100 μM of cisplatin, and survival decreased at 500 μM of cisplatin. As the cisplatin concentration increased, the accumulation of Pt in fish embryos also increased. These results revealed that hair cells are significantly more susceptible to cisplatin toxicity than ionocytes. By determining the lowest observed effective concentration of cisplatin that caused in vivo functional alterations of zebrafish hair cells and skin ionocytes, this model demonstrated 500-fold greater sensitivity than by detecting changes in survival, for early assessment of the effects of platinum-based chemotherapeutic drugs on fish.
AB - This study aimed to assess the sublethal effects of a platinum-based compound, cisplatin, using a zebrafish model. Zebrafish embryos were incubated in different concentrations of cisplatin at 0–96 h post-fertilization. Using a non-invasive, scanning ion-selective electrode technique (SIET), we measured the functions of hair cells (Ca2+ influx) and ionocytes ([H+] gradients). The survival rate, hatching rate, phenotype, body length, whole-body ion (Na+, Cl−, and Ca2+) and Pt contents were also determined. The effects of cisplatin on zebrafish embryos were demonstrated as first impairing hair cell function (at 1 μM of cisplatin), the hair cell number, and body ion content of Cl− (at 10 μM of cisplatin), then decreasing ionocyte acid secretion and overall body ion contents of Na+ and Ca2+ (at 50 μM of cisplatin). The body length and ionocyte density decreased at 100 μM of cisplatin, and survival decreased at 500 μM of cisplatin. As the cisplatin concentration increased, the accumulation of Pt in fish embryos also increased. These results revealed that hair cells are significantly more susceptible to cisplatin toxicity than ionocytes. By determining the lowest observed effective concentration of cisplatin that caused in vivo functional alterations of zebrafish hair cells and skin ionocytes, this model demonstrated 500-fold greater sensitivity than by detecting changes in survival, for early assessment of the effects of platinum-based chemotherapeutic drugs on fish.
KW - Cisplatin
KW - Hair cell
KW - Ionocyte
KW - Platinum-based
KW - Zebrafish
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U2 - 10.1016/j.aquatox.2019.02.006
DO - 10.1016/j.aquatox.2019.02.006
M3 - Article
C2 - 30784778
AN - SCOPUS:85061573223
SN - 0166-445X
VL - 209
SP - 168
EP - 177
JO - Aquatic Toxicology
JF - Aquatic Toxicology
ER -