Auditory dysfunction and cochlear vascular injury following trimethyltin exposure in the guinea pig.
Trimethyltin chloride (TMT) produces an auditory impairment in the rat due, presumably, to cochlear injury. The loss is unusual in that it persists for several weeks, but ultimately resolves at least at low to middle frequencies. Recovery of high frequency auditory loss is less predictable. Given this pattern of injury and recovery plus the known ability of TMT to impair oxidative phosphorylation, it was hypothesized that TMT would damage the stria vascularis which is the most metabolically active area and a structure containing one of the primary vascular networks in the cochlea. Trimethyltin chloride ototoxicity was evaluated in guinea pigs treated with the toxicant and then subjected to weekly tests of the auditory brainstem response evoked by tonal stimuli. A high frequency impairment was found which tended to improve within the first 2 weeks after exposure. Subjects were euthanized 6 weeks after TMT for histopathological study of the cochlea. At that time point most subjects showed full functional recovery. Subjects showed significant changes both in the number of outer hair cells and in the condition of the stria vascularis. Outer hair cell loss was observed in a restricted portion of the most basal turn of the cochlea which is responsible for encoding high frequency sound despite recovery of function in some animals. A very marked increase in the diameter of the vessels of the stria vascularis was observed along with signs of atrophy in the stria vascularis. Enlarged vessel diameters were particularly apparent in the apical and middle turns of the cochlea, which did not show significant hair cell loss. The data confirm that TMT does produce both hair cell damage and vascular pathology in the cochlea.
Fechter
L D
LD
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
Carlisle
L
L
D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000098:blood supply / Q000187:drug effects*; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D006311:Hearing Disorders / Q000139:chemically induced*; D013316:Stria Vascularis / Q000187:drug effects / Q000473:pathology; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C040533:trimethyltin chloride