[Distribution of gentamicin in inner ear after intratympanic gentamicin injection].
ABSTRACT To investigate uptake and accumulation of gentamicin by cells in the guinea pig inner ear after intratympanic injection using a fluorescent probe--gentamicin-Texas-red conjunction (GTTR).
Adult guinea pigs (n = 80) were administered a single dose of GTrR to the middle ear cavity through the intact membrane and survived for 12 h, 24 h, 48 h, 3 d, 4 d, 7 d, 14 d and 28 d. The distribution of GTTR in the cochlear and vestibular cells was observed after staining with phalloidin-alexa-488. Texas Red and DMSO were injected into the tympanum as control.
Diffuse staining of gentamicin in the labyrinth was observed initially after local drug administration. At later time point the outer hair cells and sensory cells of vestibular organ were staining more densely than the support cells in the inner ear. The peak level of fluorescent density was reached 3 days after local injection. The GTTR was observed in the infracuticular zone.
GTTR was a potential fluorescent probe to investigate the pharmacokinetics and mechanisms of gentamicin accumulation in local application.
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ABSTRACT: The amphipathic molecule dimethyl sulphoxide (DMSO) is a solvent often used to dissolve compounds applied to the inner ear; however, little is known about its potential cytotoxic side effects. To address this question, we applied 0.1-6% DMSO for 24h to cochlear organotypic cultures from postnatal day 3 rats and examined its cytotoxic effects. DMSO concentrations of 0.1% and 0.25% caused little or no damage. However, concentrations between 0.5% and 6% resulted in stereocilia damage, hair cell swelling and a dose-dependent loss of hair cells. Hair cell damage began in the basal turn of the cochlea and spread towards the apex with increasing concentration. Surprisingly, DMSO-induced damage was greater for inner hair cells than outer hair cell whereas nearby supporting cells were largely unaffected. Most hair cell death was associated with nuclear shrinkage and fragmentation, morphological features consistent with apoptosis. DMSO treatment induced TUNEL-positive staining in many hair cells and activated both initiator caspase-9 and caspase-8 and executioner caspase-3; this suggests that apoptosis is initiated by both intrinsic mitochondrial and extrinsic membrane cell death signaling pathways.Hearing Research 03/2008; 236(1-2):52-60. · 2.70 Impact Factor
Article: Comparison of gentamicin distribution in the inner ear following administration via the endolymphatic sac or round window.[show abstract] [hide abstract]
ABSTRACT: The distribution of gentamicin in the inner ear via the endolymphatic sac (ES) or round window (RW) routes was investigated. Experimental study. A fluorescent gentamicin-Texas Red conjugate (GTTR) was adopted to visualize the gentamicin. Adult guinea pigs were treated with GTTR applied to the ES or RW, the animals were allowed to recover for 3 days, then confocal microscopy was used to observe and quantify GTTR distributions in cochlear and vestibular sensory epithelium. When GTTR was applied via the ES, strong GTTR labeling was observed in the vestibule while little GTTR was detected in the cochlea (P < .0001). However, distinct GTTR fluorescence was observed in the cochlea and vestibule following RW application (P = .7967). There was less GTTR labeling in cochlea via ES application than through RW administration (P < .0001). ES drug application may be preferable for the treatment of intractable Meniere's disease. Laryngoscope, 2010.The Laryngoscope 10/2010; 120(10):2054-60. · 1.75 Impact Factor