Dexmedetomidine Preconditioning Attenuates Cisplatin-Induced Ototoxicity in Zebrafish

Abstract

ObjectivesUtilisation of high-frequency drills is known to increase noise induced hearing loss due to increasing the damages of inner ear cells. This study aimed to investigate whether preconditioning by using dexmedetomidine (DEX) decreased the occurrence of ischemia in inner cells of the ear.MethodsWe utilised a transgenic zebrafish line Brn3C, and the embryos were collected from breeding adult zebrafish. Five-day-old larvae were cultured at the density of 50 embryos, and the larvae were classified into 4 groups: control, cisplatin group, DEX group, and DEX+yohimbine; adrenoreceptor blocker group. The DEX group was categorised into 3 subgroups by dosage; 0.1, 1, and 10 µM. Preconditioning was performed for 150 minutes and then exposed to cisplatin for 6 hours. The experiment was performed in 7 replicates for each group and the number of hair cells in 3 parts of the neuromasts of each fish was determined.ResultsHair cell apoptosis by cisplatin was attenuated more significantly in the DEX preconditioning group than in the control group. However, the preconditioning effects were not blocked by yohimbine.ConclusionThe results of this study suggest that hearing loss caused by vibration-induced noise could be reduced by using DEX and may occur through other mechanisms rather than adreno-receptors.

Use of zebrafish larvae lateral line to study protection against cisplatin-induced ototoxicity: A scoping review

“…Rapamycin and SRT1720 protected the lateral line of larval zebrafish against 12 h exposure to 600 µM cisplatin. 17 , 28 , 31 , 34 , 38 , 40 The proteasome inhibitor (Z-LLF-CHO) protected from the exposure to 750 μM cisplatin but had no effect when the lower concentration of cisplatin was used. 31 The curcuminoids offered protection against a single cisplatin injection (25 mg/kg).…”

“…In agreement with the above notion, the otoprotective action of dexmedetomidine, edaravone, KR-22335, apocynin, ATX-LPN, quercetin, and the CHCP1 and CHCP2 molecules were related to their ability to decrease ROS production. 17 , 20 , 23 , 26 Similarly, the EF-24 was suggested to prevent intracellular ROS formation via inhibition of NF-kB-induced signaling and suppressed expression of oncogenic miRNAs, including miR-21. 33 Also dimethyl sulfoxide (DMSO) used at low concentrations is a known scavenger of the hydroxyl radicals.…”

“…The first EM was composed of 15.0 mM NaCl, 0.5 mM KCl, 1.0 mM MgSO 4 , 0.12 mM KH 2 PO 4 , 0.074 mM Na 2 HPO 4 , 1.0 mM CaCl 2 , 0.5 mM NaHCO 3 in distilled water. [17][18][19][20][21][22][23][24][25][26][27][28] The second EM was compsed of 14.9 mM NaCl, 0.503 mM KCl, 0.994 mM MgSO 4 , 0.150 mM KH 2 PO 4 , 42 mM Na 2 HPO 4 , 0.986 mM CaCl 2 , 0.714 mM NaHCO 3 in distilled water. 12,[29][30][31]32,33 In addition, the embryos were also kept in E3 embryo media consisting of 5 mM NaCl, 0.17 mM KCl, 0.33 mM CaCl 2 , 0.33 MgSO 4 or in a standard bath solution containing: 120 mM NaCl, 2 mM KCl, 10 mM HEPES (2-[4-(2-hydroxyethyl) piperazin-1-yl]ethanesulfonic acid), 2 mM CaCl2 and 0.7 mM NaH2PO4 adjusted to pH 7.2.…”

“…12,19,31,34,38 The last experimental strategy consisted of preconditioning with otoprotective medication (dexmedetomidine, KR-22335, CHCP1, CHCP2, ATX) and later a sole exposure to cisplatin. 17,26,27,40 In one experimental protocol using adult zebrafish, a single microinjection of cisplatin and drug was applied, whereas when cell cultures were used, the experimental procedure included incubation with cisplatin and then co-incubation with the otoprotective substances. 33,35,36 In the studies dedicated to apocynin, L-Serine, CHCP1, Rapamycin, Sal B, KR-22335, ORC-13661, ATX, NAC, CYM-5478, and curcuminoids zebrafish served as a second model in addition to mice, guinea pig, cancer cell lines and HEI-OC1 mouse cell line derived from the organ of Corti.…”

“…33,35,36 In the studies dedicated to apocynin, L-Serine, CHCP1, Rapamycin, Sal B, KR-22335, ORC-13661, ATX, NAC, CYM-5478, and curcuminoids zebrafish served as a second model in addition to mice, guinea pig, cancer cell lines and HEI-OC1 mouse cell line derived from the organ of Corti. 17,20,27,28,30,35,[38][39][40] The details regarding the experimental design for otoprotective screening are summarized in Table 2.…”