In vitro and animal studies of sodium thiosulfate as a potential chemoprotectant against carboplatin-induced ototoxicity

Edward A. Neuwelt, Robert E. Brummett, Laura G. Remsen, Robert A. Kroll, Michael A. Pagel, Christopher I. McCormick, Sydney Guitjens, Leslie L. Muldoon

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)706-709
Number of pages4
JournalCancer Research
Volume56
Issue number4
StatePublished - Feb 15 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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