Comparative study of ototoxicity between kanamycin and 2-hydroxypropyl-β-cyclodextrin
YANG Kun, CHEN Lijuan, HE Xiaodan, LIU Zhiqi, SHA Suhua
Journal of Otolaryngology and Ophthalmology of Shandong University
2022, 36 ( 4):
Objective This study aimed to investigate the effects of ototoxic injury induced by kanamycin and 2-hydroxypropyl-β-cyclodextrin(HPβCD)in CBA/J mice. Methods Male CBA/J mice were intraperitoneally administered kanamycin for 15 days at the optimal dosage of 700 mg/kg and were subcutaneously administered HPβCD at the optimal dosage of 8 000 mg/kg. The control group was administered 0.9 % sterile sodium chloride. Auditory brainstem response tests were performed. Cochlear preparations and diaminobenzidine staining were used for hair cell observation. Data were analyzed using the statistical software GraphPad Prism 13 for Windows. Results In the control group, at 8 kHz, 16 kHz, and 32 kHz, the thresholds were 21±2.24 dB, 21±2.24 dB, and 21±2.24 dB, respectively. After kanamycin treatment, the thresholds were 22±2.74 dB( t=0 .632 5 , P=0.544 7), 67± 4.47 dB( t=20 .571 8 , P<0.001), and 77±4.47 dB( t=25 .044 0 , P<0.001), respectively. After 6 hours, the thresholds in the HPβCD group were 29±4.18 dB, 30±4.47 dB, and 37±2.74 dB, respectively. After 7 hours, the thresholds were 65±3.54 dB, 71±2.24 dB, and 80±3.54 dB, and after 8 hours, the thresholds were 70±3.54 dB, 78±5.70 dB, and 85±5.00 dB, respectively. Comparison of the data revealed significant differences( F=20 .590 , P<0.001). Prolonging HPβCD treatment resulted in hearing loss being gradually aggravated at all frequencies. In the kanamycin group, outer hair cell(OHC)loss from the top to the base was significantly different( F=7 .840 , P=0.000 3), with 9.17±6.03% at 2.0 mm, 89.76±3.12% at 2.5 mm, and 100% at 4.0 mm. Inner hair cell(IHC)loss was also significantly different( F=3 .549 , P<0.05), with values of 0.71±0.00%, 6.79±6.01%, and 20.71±6.00% being recorded. Six hours of HPβCD treatment resulted in obvious damage to OHCs of the cochlea. Damage occurred at the apex, the middle, and the base of the basement membrane. After 7 to 8 hours, the IHCs and OHCs had practically disappeared. After 8 hours, no IHCs were found. Conclusion Kanamycin and HPβCD induced hearing loss and hair cell damage in mice. OHC damage occurred earlier than the IHC damage, with the degree of damage being dependent on the time and concentration of treatment.The difference is that Kanamycin damaged hearing at the onset of high frequencies, while HPβCD starts from full frequency.
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