Combined Effects of Low-Dose Kanamycin and Noise Exposure on Auditory Brainstem Response and Cochlear Microphonic Potential in Guinea Pigs Synergistic Effects of Noise and Kanamycin on Auditory Brainstem
Iranian Journal of Child Neurology,
Vol. 20 No. 2 (2026),
1 April 2026
,
Page 13-20
https://doi.org/10.22037/ijcn.v20i2.50974
Abstract
Objectives:
Aminoglycoside‑induced ototoxicity is a well‑recognized adverse effect that commonly presents as sensorineural hearing loss. This study investigated hearing damage by administering two doses of Kanamycin, with or without concurrent noise exposure. Auditory function was assessed using auditory brainstem response and cochlear microphonic potential.
Materials & Methods:
Guinea pigs were divided into six groups: Control, Noise exposure, Kanamycin 300 mg/kg alone (low dose), Kanamycin 300 mg/kg + Noise, Kanamycin 500 mg/kg alone (high dose), and Kanamycin 500 mg/kg + Noise. Auditory threshold shifts were evaluated using click and pure tones at 4, 6, 8, 12, and 16 kHz. The cochlear microphonic amplitude was measured before and after intervention in the study groups. The latency and amplitude of waves I and III were analyzed in the groups without sensorineural hearing loss.
Results:
Auditory threshold shifts were significantly greater in the low-dose Kanamycin + noise group compared to both the low-dose Kanamycin alone and the noise-only groups across all stimuli (p < 0.05). In contrast, the high-dose Kanamycin alone and the high-dose Kanamycin + noise groups exhibited similar thresholds. They demonstrated significantly higher thresholds than the noise-only group (p < 0.05). Furthermore, no significant difference in the cochlear microphonic amplitude was found among the study groups.
Conclusion:
Kanamycin at low doses is not inherently ototoxic; however, when combined with noise exposure, it produces a synergistic effect resulting in severe hearing loss. In this model of auditory damage, cochlear microphonic measurements are less informative than auditory brainstem response testing, providing a more reliable assessment of both peripheral and central auditory pathway function.
- auditory brain stem response
- kanamycin
- Hearing loss
- Cochlear microphonic potentials
How to Cite
References
1. Han L, Wang Z, Wang D, Gao Z, Hu S, Shi D, et al. Mechanisms and otoprotective strategies of programmed cell death on aminoglycoside-induced ototoxicity. Front Cell Dev Biol 2024;11:1305433.
2. Prasad K, Borre ED, Dillard LK, Ayer A, Der C, Bainbridge KE, et al. Priorities for hearing loss prevention and estimates of global cause-specific burdens of hearing loss: a systematic rapid review. Lancet Glob Health 2024;12(2):e217–e25.
3. Rivetti S, Romano A, Mastrangelo S, Attinà G, Maurizi P, Ruggiero A. Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients. Pharmaceuticals (Basel) 2023;16(10).
4. Chen J, Liu Z, Yan H, Xing W, Mi W, Wang R, et al. miR-182 prevented ototoxic deafness induced by co-administration of kanamycin and furosemide in rats. Neurosci Lett 2020;723:134861.
5. Deng X, Liu Z, Li X, Zhou Y, Hu Z. Generation of new hair cells by DNA methyltransferase (Dnmt) inhibitor 5-azacytidine in a chemically-deafened mouse model. Sci Rep 2019;9(1):7997.
6. Hildebrand MS, Dahl H-HM, Hardman J, Coleman B, Shepherd RK, De Silva MG. Survival of partially differentiated mouse embryonic stem cells in the scala media of the guinea pig cochlea. J Assoc Res Otolaryngol 2005;6(4):341–54.
7. Bako P, Gerlinger I, Wolpert S, Mueller M, Loewenheim H. The ototoxic effect of locally applied kanamycin and furosemide in guinea pigs. J Neurosci Methods 2022;372:109527.
8. Shimada MD, Noda M, Koshu R, Takaso Y, Sugimoto H, Ito M, et al. Macrophage depletion attenuates degeneration of spiral ganglion neurons in kanamycin-induced unilateral hearing loss model. Sci Rep 2023;13(1):16741.
9. Salgueiro SR, Núñez LG. Animal models mimicking aminoglycoside-induced renal damage. J Nephropharmacol 2016;5(1):1.
10. Jiang M, Karasawa T, Steyger PS. Aminoglycoside-induced cochleotoxicity: a review. Front cell neurosci 2017;11:308.
11. Mahdi P, Pourbakht A, Mahabadi VP, Yazdi AK, Anari MR, Kamali M. Cochlear Synaptopathy Following Noise Exposure in Guinea Pigs: Its Electrophysiological and Histological Assessments. SV 2020;54(3).
12. Ohlemiller KK, Rice MER, Rosen AD, Montgomery SC, Gagnon PM. Protection by low-dose kanamycin against noise-induced hearing loss in mice: dependence on dosing regimen and genetic background. Hear Res 2011;280(1-2):141–47.
13. POURBAKHT A, KAMRAVA SK, KAMALI M, YOUSEFI A. Comparison of cochlear microphonics magnitude with broad and narrow band stimuli in healthy adult wistar rats. Iran J Child Neurol 2018;12(2):58.
14. Starr A, Sininger Y, Nguyen T, Michalewski H, Oba S, Abdala C. Cochlear receptor (microphonic and summating potentials, otoacoustic emissions) and auditory pathway (auditory brain stem potentials) activity in auditory neuropathy. Ear Hear 2001;22(2):91–99.
15. Mahdi P, Pourbakht A, Yazdi AK, Anari MR, Mahabadi VP, Kamali M. Metabotropic glutamate receptor: A new possible therapeutic target for cochlear synaptopathy. Iran J Basic Med Sci 2022;25(1):75.
16. Fernandez EA, Ohlemiller KK, Gagnon PM, Clark WW. Protection against noise-induced hearing loss in young CBA/J mice by low-dose kanamycin. J Assoc Res Otolaryngol 2010;11(2):235–44.
17. Nitta Y, Kurioka T, Mogi S, Sano H, Yamashita T. Suppression of the TGF-β signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice. Sci Rep 2024;14(1):10910.
18. Ruel J, Wang J, Rebillard G, Eybalin M, Lloyd R, Pujol R, et al. Physiology, pharmacology and plasticity at the inner hair cell synaptic complex. Hear Res 2007;227(1-2):19–27.
19. Liu K, Jiang X, Shi C, Shi L, Yang B, Shi L, et al. Cochlear inner hair cell ribbon synapse is the primary target of ototoxic aminoglycoside stimuli. Mol Neurobiol 2013;48(3):647–54.
20. Shi L, Chang Y, Li X, Aiken S, Liu L, Wang J. Cochlear Synaptopathy and Noise‐Induced Hidden Hearing Loss. Neural Plast 2016;2016(1):6143164.
21. Lee CH, Lee SM, Kim SY. Telmisartan attenuates kanamycin-induced ototoxicity in rats. Int J Mol Sci 2021;22(23):12716.
22. Zhang Y, Huang S, Dai X, Xia Z-f, Xiao H, He X-l, et al. SOD2 alleviates hearing loss induced by noise and kanamycin in mitochondrial DNA4834-deficient rats by regulating PI3K/MAPK signaling. Curr Med Sci 2021;41(3):587–96.
23. Park J-E, Kim WC, Kim SK, Ahn Y, Ha SM, Kim G, et al. Protection of hearing loss in ototoxic mouse model through SPIONs and dexamethasone-loaded PLGA nanoparticle delivery by magnetic attraction. Int J Nanomedicine 2022;17:6317.
24. Charaziak K, Shera C, Siegel J. Using Cochlear Microphonic Potentials to Localize Peripheral Hearing Loss. Front. Neurosci 2017; 11:169. 2017.
25. Frost B, Olson ES. Model of cochlear microphonic explores the tuning and magnitude of hair cell transduction current. Biophys J 2021;120(17):3550–65.
26. Chen L, Trautwein PG, Miller K, Salvi RJ. Effects of kanamycin ototoxicity and hair cell regeneration on the DC endocochlear potential in adult chickens. Hear Res 1995;89(1-2):28–34.
27. Pedemonte M, Drexler DG, Velluti RA. Cochlear microphonic changes after noise exposure and gentamicin administration during sleep and waking. Hear Res 2004;194(1-2):25–30.
- Abstract Viewed: 71 times