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Histological evaluation of ototoxic reaction due to some aminoglycoside antibiotics
Abstract:
Twenty-one days s.c. treatment with netilmicin, gentamicin, sisomicin, and kanamicin at different doses were performed in albino guinea pigs of both sexes. Block surface preparation of Corti's organ was carried out and missing OHCs and IHCs counted in selected areas of each turn. The animals treated with gentamicin and sisomicin showed a dose-depending missing of hair cells, preferably relative to the outer ones and quantitatively the same for both the antibiotics. Furthermore, a characteristic distribution of the damage progressively increasing from the apex to the basal turn of the cochlea was detected. Kanamicin at 267 and 400 mg/kg gave the complete destruction of OHCs and IHCs along the whole cochlea while at 178 mg/kg did not show any significant damage in comparison to the control group. Finally, netilmicin neither damaged Corti's organ nor statistically determined missing OHCs and IHCs at all the doses used. These histological results and the previous electrophysiological and reflexological observations obtained in the guinea pig show a higher safety of netilmicin in comparison to the other aminoglycosides used for the problem relative to ototoxicity.
Insights
Netilmicin demonstrated superior safety compared to gentamicin, sisomicin, and kanamycin in guinea pigs. This study assessed ototoxicity by examining hair cell damage in the cochlea after aminoglycoside treatment.
Area of Science:
- Ototoxicology
- Pharmacology
- Histopathology
Background:
- Aminoglycosides are crucial antibiotics but can cause ototoxicity.
- Assessing the ototoxic potential of different aminoglycosides is vital for clinical safety.
Purpose of the Study:
- To histologically compare the ototoxicity of netilmicin, gentamicin, sisomicin, and kanamycin in a guinea pig model.
- To determine dose-dependent and location-specific hair cell damage induced by these antibiotics.
Main Methods:
- Guinea pigs received daily subcutaneous injections of netilmicin, gentamicin, sisomicin, or kanamycin for 21 days.
- Hair cell loss (outer hair cells and inner hair cells) in Corti's organ was quantified.
- Damage was assessed across different cochlear turns (apical, middle, basal).
Main Results:
- Gentamicin and sisomicin induced dose-dependent hair cell loss, primarily affecting outer hair cells, with damage increasing from apex to base.
- Kanamycin at higher doses (267 and 400 mg/kg) caused complete destruction of outer and inner hair cells.
- Netilmicin showed no significant hair cell damage at any tested dose.
Conclusions:
- Netilmicin exhibits a significantly better ototoxicity profile compared to gentamicin, sisomicin, and kanamycin.
- The findings support netilmicin's higher safety margin for clinical use, minimizing the risk of hearing loss.