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Gentamicin ototoxicity in otoconia: quantitative electron probe X-ray microanalysis
A Campos1, J A López-Escámez, P V Crespo
1Department of Histology and Cell Biology, Faculty of Medicine, University of Granada, Spain.
Abstract:
Chronic gentamicin ototoxicity was evaluated in the otolithic membrane of adult OF1 mice at the otoconial layer of the saccule and utricle by quantitative electron probe X-ray microanalysis of Ca and K. The otolithic membranes were plunge-frozen and freeze-dried. The analysis was carried out with an energy dispersive detector using the peak-to-back-ground ratio method and different inorganic salts of Ca and K as standards to calibrate the microprobe. Ca and K in the otoconia are related via a linear function in both the saccule and the utricle. This association is not maintained after exposure to gentamicin, which suggests that this aminoglycoside antibiotic interferes with the Ca-K equilibrium in the otoconia. A dose of 200 mg/kg gentamicin twice a day for 5 days did not affect Ca in the mineral phase of the otoconia, but did increase K in both saccular (p < 0.05) and utricular (p < 0.01) otoconia. These increases in K may reflect a modification in the composition of the endolymph, resulting from cellular damage at the plasma membrane.
Insights
Gentamicin exposure disrupts the calcium-potassium balance in mouse otoconia, the sensory structures of the inner ear. This aminoglycoside antibiotic alters otoconial composition, potentially impacting balance and hearing functions.
Area of Science:
- Ototoxicity research
- Inner ear physiology
- Biomineralization
Background:
- Gentamicin, an aminoglycoside antibiotic, is known to cause ototoxicity.
- The otolithic membrane, containing otoconia, is crucial for balance and hearing.
- The ionic composition of otoconia, particularly calcium and potassium, is vital for their function.
Purpose of the Study:
- To investigate the effects of chronic gentamicin exposure on the calcium and potassium content in the otolithic membrane of adult OF1 mice.
- To determine if gentamicin disrupts the established relationship between calcium and potassium in otoconia.
Main Methods:
- Quantitative electron probe X-ray microanalysis was used to measure Ca and K levels in the otoconial layer of the saccule and utricle.
- Otolithic membranes were plunge-frozen and freeze-dried before analysis.
- The peak-to-background ratio method with inorganic salt standards was employed for microprobe calibration.
Main Results:
- A linear relationship between Ca and K was observed in otoconia from control mice.
- Gentamicin exposure did not alter Ca levels in the mineral phase of otoconia.
- A significant increase in K was detected in both saccular (p < 0.05) and utricular (p < 0.01) otoconia after gentamicin treatment.
Conclusions:
- Chronic gentamicin exposure interferes with the Ca-K equilibrium in otoconia.
- Increased K in otoconia may indicate alterations in endolymph composition due to gentamicin-induced cellular damage.
- These findings suggest a potential mechanism for gentamicin-induced hearing and balance dysfunction.