Protective effects of Y-27632 against cisplatin-induced ototoxicity: A zebrafish model Y-27632 and cisplatin-induced ototoxicity.

Cisplatin is an effective chemotherapy agent against various solid malignancies; however, it is associated with irreversible bilateral sensorineural hearing loss, emphasizing the need for drug development to prevent this complication, with the current options being very limited. Rho-associated coiled-coil-containing protein kinase (ROCK) is a serine-threonine protein kinase involved in various cellular processes, including apoptosis regulation. In this study, we used a transgenic zebrafish model (Brn3C: EGFP) in which hair cells within neuromasts are observed in green under fluorescent microscopy without the need for staining. Zebrafish larvae were exposed to cisplatin alone or in combination with various concentrations of Y-27632, a potent ROCK inhibitor. Hair cell counts, apoptosis assessments using the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay, FM1-43FX labeling assay and behavioral analyses (startle response and rheotaxis) were performed to evaluate the protective effects of Y-27632 against cisplatin-induced ototoxicity. Cisplatin treatment reduced the number of hair cells in neuromasts, induced apoptosis, and impaired zebrafish larval behaviors. Y-27632 demonstrated a dose-dependent protective effect against cisplatin-induced hair cell loss and apoptosis. These findings suggest that Y-27632, as a ROCK inhibitor, mitigates cisplatin-induced hair cell loss and associated ototoxicity in zebrafish.

Auditory brainstem response test results in normal hearing adolescents with subjective tinnitus.

OBJECTIVES: The objective of the study was to analyze the auditory brainstem response (ABR) test results of adolescents with normal hearing threshold who have subjective tinnitus in an effort to determine the probable site of origin of tinnitus. METHODS: Among the patients who visited the outpatient clinic of the Department of Otolaryngology at our tertiary hospital from January 2016 to December 2019, adolescents aged 13-18 years with the chief complaint of unilateral subjective tinnitus and pure tone audiometry (PTA) within 25 dB HL were enrolled and retrospectively reviewed. The ABR test parameters (amplitudes and latencies of waves I, III, and V and interpeak latencies [IPLs] of waves I-III, III-V, and I-V) were analyzed and compared between tinnitus ears and contralateral ears without tinnitus. Study participants were divided into the chronic tinnitus (tinnitus duration ≥6 months) and non-chronic tinnitus (tinnitus duration <6 months) groups, and the difference between the two groups was analyzed. RESULTS: Ten adolescents were included in the study, and their ABR test results were reviewed. IPL III-V was significantly prolonged in tinnitus ears compared to non-tinnitus ears (p = 0.035). Although other parameters were found to be statistically non-significant, there was preponderance in ABR wave I amplitude; it was smaller in tinnitus ears of chronic tinnitus adolescents than in those of non-chronic tinnitus adolescents (p = 0.114). CONCLUSION: The probable site of origin of tinnitus in adolescents with normal hearing might be in the upper brainstem of the auditory pathway. Further analysis of ABR test results in adolescents with tinnitus and normal hearing can help clarify the pathophysiology of tinnitus in adolescents.

Analysis of behavioral changes in zebrafish (Danio rerio) larvae caused by aminoglycoside-induced damage to the lateral line and muscles.

Zebrafish behavior is influenced by the lateral line hair cells and muscles. Drug-induced behavioral changes can serve as indicators in the evaluation of drug toxicity. The aminoglycoside family of antibiotics comprise a number of agents, including neomycin (NM) and gentamicin (GM). We hypothesized that NM and GM exert different effects on zebrafish larvae through their action on the lateral line and muscle fibers, inducing different swimming behavioral patterns such as locomotor behavior and the startle response. In this study, 125 µM NM and 5, 10, 20 µM GM induced hair cell damage in the anterior and posterior lateral lines of zebrafish larvae. However, unlike GM, 125 µM NM also caused muscle damage. Locomotor behavior was decreased in the 125 µM NM-exposed group compared to the group exposed to GM. Furthermore, 125 µM NM exposure induced significantly different patterns of various indices of startle behavior compared with the GM exposure groups. Additionally, the larvae exhibited different startle responses depending on the concentration of GM. These results suggest that GM may be the drug-of-choice for analyzing behavioral changes in zebrafish caused by damage to the lateral line alone. Our study highlights the importance of confirming muscle damage in behavioral analyses using zebrafish.

Assessment of hair cell damage and developmental toxicity after fine particulate matter 2.5 µm (PM 2.5) exposure using zebrafish (Danio rerio) models.

OBJECTIVES: Particulate matter (PM) exposure has become one of the most serious problems. The aim of the present study was to evaluate the hair cell damage and possible developmental toxicity caused by PM2.5 exposure using a zebrafish model. METHODS: Zebrafish embryos were exposed to various concentrations of PM2.5. Developmental toxicity was evaluated based on general morphology score (GMS) system and Panzica-Kelly score, and by measurement of body length and heart rate. To evaluate hair cell damage, the average number of total hair cells within four neuromasts exposed to various concentrations of PM2.5 was compared with that of the control group. RESULTS: Morphological abnormalities evaluated by the GMS system and Panzica-Kelly score were rare and body length tended to be shorter in the PM2.5-exposed groups. Heart rate decreased significantly in the PM2.5-exposed group. Additionally, significant hair cell damage was observed after PM2.5 exposure. It was dose-dependent and more severe after a longer period exposure (10 dpf). CONCLUSIONS: In zebrafish embryos, exposure of PM2.5 in the early stages of life decreased heart rate and caused significant hair cell damage in a dose-dependent manner.