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Updated: May 24, 2026

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Aminoglycosides: therapeutics, ototoxicity and hypersensitivity of mitochondrial genetic origin
N M Torres-Ruíz1, O Granados, G Meza
1Departamento Neuropatología Molecular, Instituto de Fisiologio Celular, UNAM.
Abstract:
Aminoglycosides such as streptomycin or gentamycin are employed to treat stubborn infections. In México, tuberculosis patients are successfully treated with 1 g/day for over 6 months. Ototoxicity is often seen as a consequence of prolonged treatment with aminoglycosides. In young people STP damages the vestibule of the ear; in elder patients it diminishes hearing and balance. These effects are due to streptidine, a metabolite of STP produced in elder patients and detected in blood by liquid chromatography. On occasion, sudden deafness is established after only a short treatment period as the result of the presence of a single nucleotide mutation in the mitochondrial 12S rRNA gene. In patients with this polymorphism, aminoglycosides produce a stereotypic conformation similar to the bacterial 16S rRNA thus inhibiting the synthesis of proteins. Many aminoglycoside-sensitive mutations have been described in several ethnic groups, causing sudden deafness. We started similar studies in Mexican individuals, treated or not with an aminoglycoside, to determine whether similar alterations could be detected. To date in over 60 individuals analyzed we found only one case of polymorphism in a streptomycin treated patient. We developed a simple method to identify such mitochondrial gene in a larger population to make recommendations to use an alternative treatment which do not cause ototoxicity in the mutation bearing patient.
Insights
Aminoglycoside antibiotics can cause hearing loss due to genetic mutations. Researchers developed a method to identify these mutations in Mexican patients, aiming to prevent ototoxicity and recommend alternative treatments.
Area of Science:
- Pharmacogenomics
- Ototoxicology
- Molecular Biology
Background:
- Aminoglycosides, like streptomycin, are vital for treating infections such as tuberculosis.
- Ototoxicity, including hearing loss and balance issues, is a significant side effect of prolonged aminoglycoside use.
- A specific mitochondrial 12S rRNA gene mutation predisposes individuals to sudden deafness from aminoglycosides.
Purpose of the Study:
- To investigate the prevalence of aminoglycoside-associated ototoxicity-related genetic mutations in the Mexican population.
- To develop a screening method for identifying at-risk individuals.
- To enable personalized treatment recommendations to prevent aminoglycoside-induced ototoxicity.
Main Methods:
- Analysis of mitochondrial 12S rRNA gene in Mexican individuals.
- Liquid chromatography to detect streptidine metabolite in elder patients.
- Development of a simple method for identifying the specific mitochondrial gene mutation.
Main Results:
- Only one case of the relevant mitochondrial gene polymorphism was detected in over 60 Mexican individuals analyzed.
- The identified polymorphism was found in a patient treated with streptomycin.
- A simple method for identifying the mutation in a larger population was successfully developed.
Conclusions:
- The prevalence of this specific ototoxicity-related mutation appears low in the studied Mexican population.
- The developed screening method can facilitate the identification of individuals susceptible to aminoglycoside ototoxicity.
- This research paves the way for personalized treatment strategies to mitigate hearing loss in susceptible patients.
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