Publication: Streptidine, a metabolic derivative produced after administration
of streptomycin in vivo, is vestibulotoxic in rats
Authors
Granados, O. ; Meza Ruiz, G.
item.page.secondaryauthor
item.page.director
Publisher
Murcia : F. Hernández
publication.page.editor
publication.page.department
DOI
item.page.type
info:eu-repo/semantics/article
Description
Abstract
Streptomycin is the treatment of choice in
developing countries for patients suffering from
tuberculosis or other infectious diseases. However, it
produces incapacitating vestibular symptoms whose
onset is delayed and gradual. This observation led to the
notion that a streptomycin metabolic derivative and not
the antibiotic itself is the damaging agent for the inner
ear.
To study further the existence of this ototoxic
metabolite, chronic treatment with streptomycin or its
putative derivative streptidine was carried out in young
male Long Evans rats. The presence of streptomycin or
streptidine in the blood of animals of either experimental
group was assessed by high performance liquid
chromatography and analysis of swimming behavior was
used to evaluate vestibular damage. Features of the
sensory epithelium and quantification of hair cells were
attained in sections of the utricular organ of all groups
by light microscopy.
After 25, 35 and 45 days of treatment with
streptomycin, a metabolite with the same
chromatographic properties as the streptidine standard
run in parallel was identified in the blood of rats.
Concentrations of the metabolite were 2.26 µg/ml on the
25th day and around 8.0 µg/ml in both the 35th and the 45th day of treatment, while streptomycin was below its
detection level at either period. In streptidine-treated
rats, the concentration of this compound was 1.0, 1.84
and 4.94 µg/ml on the 25th, 35th and 45th treatment days,
respectively. Treatment with either streptomycin or
streptidine resulted in similar abnormal swimming
patterns and histological alterations of the utricular
epithelium. Loss of hair cells was roughly equivalent
even though streptidine was administered in a dose 90%
lower than streptomycin.
The gradual appearance of streptidine as a metabolic derivative of the antibiotic in the blood of rats or the
administration of this compound alone, causing similar
functional and structural vestibular deterioration seen in
streptomycin-treated animals, supports the notion that
streptidine is a potential contributor to ototoxicity after
prolonged antibiotic administration.
publication.page.subject
Citation
item.page.embargo
Ir a Estadísticas
Sin licencia Creative Commons.