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In Vitro and Animal Studies of Sodium Thiosulfate as a Potential Chemoprotectant against Carboplatin-induced Ototoxicity¹

Departments of Neurology [E. A. N., L. G. R., R. A. K.], Biochemistry and Molecular Biology [E. A. N.], Pharmacology [R. E. B., S. G.], and Cell and Developmental Biology [L. L. M.], and Division of Neurosurgery [E. A. N.], Oregon Health Sciences University; Department of Otolaryngology, Oregon Hearing Research Center [R. E. B., S. G.]; and Veteras Administration Medical Center [E. A. N., M. A. P., C. I. M.], Portland, Oregon 97201

When carboplatin (cis-diammine-1,1-cyclobutane-dicarboxylato-platinum) delivery to brain tumors is optimized with osmotic blood-brain barrier disruption (BBBD), high frequency hearing loss can result. Treatment with sodium thiosulfate (STS) blocked carboplatin cytotoxicity against the LX-1 human small cell lung carcinoma cell line in vitro. STS decreased carboplatin-induced ototoxicity in a guinea pig model, as determined by electrophysiological measurements and analysis of inner ear outer hair cell numbers. Protection was found when STS was administered up to 8 h subsequent to carboplatin but not 24 h after carboplatin. In a rat model of osmotic BBBD, STS was neurotoxic when given immediately after BBBD but not when given 60 min after BBBD, when the barrier is reestablished. Thus, delayed administration of STS may provide a mechanism to reduce the cochlear toxicity caused by BBBD-enhanced carboplatin delivery to the brain.

¹ Financial support for this work was provided by a Veterans Administration Merit Review Grant and by Grant CA31770 from the National Cancer Institute and Grant NS33618 from the National Institute of Neurological Disorders and Stroke (all to E. A. N.), and by the U.S. Department of Education, Grant H235K30001, Program to Further the Rehabilitation of Individuals with Significant Hearing Loss (to R. E. B.).

² To whom requests for reprints should be addressed, at Oregon Health Sciences University, L603, 3181 SW Sam Jackson Park Road, Portland OR 97201.

Received 11/15/95. Accepted 1/ 2/96.

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