简介：Trimethyltin(TMT)isanoccupationalandenvironmentalhealthhazardbehavingasapotentneurotoxinknowntoaffectthecentralnervoussystemaswellastheperipheralauditorysystem.However,themechanismsunderlyingTMT-inducedototoxicityarepoorlyunderstood.ToelucidatetheeffectsofTMTonthecochlea,asingleinjectionof4or8mg/kgTMTwasadministeredintraperitoneallytoadultrats.Thecompoundactionpotential(CAP)thresholdwasusedtoassessthefunctionalstatusofthecochleaandhistologicaltechniqueswereusedtoassesstheconditionofthehaircellsandauditorynervefibers.TMTat4mg/kgproducedatemporaryCAPthresholdelevationof25-60dBthatrecoveredby28dpost-treatment.Althoughtherewasnohaircelllosswiththe4mg/kgdose,therewasanoticeablelossofauditorynervefibersparticularlybeneaththeinnerhaircells.TMTat8mg/kgproducedalargepermanentCAPthresholdshiftthatwasgreatestatthehighfrequencies.TheCAPthresholdshiftwasassociatedwiththelossofouterhaircellsandinnerhaircellsinthebasal,high-frequencyregionofthecochlea,considerablelossofauditorynervefibersandasignificantlossofspiralganglionneuronsinthebasalturn.Spiralganglionneuronsshowedevidenceofsomashrinkageandnuclearcondensationandfragmentation,morphologicalfeaturesofapoptoticcelldeath.TMT-induceddamagewasgreatestinthehigh-frequency,basalregionofthecochleaandthenervefibersbeneaththeinnerhaircellswerethemostvulnerablestructures.