Trimethyltin ototoxicity: evidence for a cochlear site of injury.
The environmental contaminant, trimethyltin (TMT), produces a profound elevation in tone intensity necessary to inhibit the acoustic startle reflex in laboratory animals which recovers over a prolonged period except at very high frequencies. The recovery that is observed does not begin until 3 to 5 weeks after a single acute administration depending upon dosage. As opposed to the very temporary threshold shifts by the salicylates and loop diuretics or the permanent and progressive ototoxicity resulting from aminoglycoside antibiotics the time course for recovery of acoustic startle reflex inhibition after TMT appears to be an anomaly for a chemical ototoxicant. In terms of the duration of loss only, this pattern appears similar to that sometimes observed after noise exposure. The current investigation replicates the finding that recovery of acoustic startle reflex inhibition after TMT is frequency related in that only the highest frequency impairment appears to be permanent. While this frequency dependence suggests a cochlear locus of injury, both the known neurotoxic effects of TMT and the time course of the behavioral impairment suggest a more central locus of injury. Compound action potential and cochlear microphonic recordings made from the round window in the current study confirm a preferential high frequency effect of TMT and demonstrate a significant cochlear component to the ototoxic effects of this agent.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects*; D003051:Cochlea / Q000187:drug effects*; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013216:Reflex, Startle / Q000187:drug effects; D013997:Time Factors; D014220:Trialkyltin Compounds / Q000009:adverse effects*; D014298:Trimethyltin Compounds / Q000009:adverse effects*
D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C040533:trimethyltin chloride