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

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

Research output: Contribution to journalArticle

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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

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Cyclobutanes
Platinum
Blood-Brain Barrier
Outer Auditory Hair Cells
High-Frequency Hearing Loss
Cochlea
Small Cell Lung Carcinoma
Inner Ear
Brain Neoplasms
sodium thiosulfate
In Vitro Techniques
Guinea Pigs
Cell Count
Cell Line
Brain

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

In vitro and animal studies of sodium thiosulfate as a potential chemoprotectant against carboplatin-induced ototoxicity. / Neuwelt, Edward; Brummett, Robert E.; Remsen, Laura G.; Kroll, Robert A.; Pagel, Michael A.; McCormick, Christopher I.; Guitjens, Sydney; Muldoon, Leslie.

In: Cancer Research, Vol. 56, No. 4, 15.02.1996, p. 706-709.

Research output: Contribution to journalArticle

Neuwelt, E, Brummett, RE, Remsen, LG, Kroll, RA, Pagel, MA, McCormick, CI, Guitjens, S & Muldoon, L 1996, 'In vitro and animal studies of sodium thiosulfate as a potential chemoprotectant against carboplatin-induced ototoxicity', Cancer Research, vol. 56, no. 4, pp. 706-709.
Neuwelt E, Brummett RE, Remsen LG, Kroll RA, Pagel MA, McCormick CI et al. In vitro and animal studies of sodium thiosulfate as a potential chemoprotectant against carboplatin-induced ototoxicity. Cancer Research. 1996 Feb 15;56(4):706-709.
Neuwelt, Edward ; Brummett, Robert E. ; Remsen, Laura G. ; Kroll, Robert A. ; Pagel, Michael A. ; McCormick, Christopher I. ; Guitjens, Sydney ; Muldoon, Leslie. / In vitro and animal studies of sodium thiosulfate as a potential chemoprotectant against carboplatin-induced ototoxicity. In: Cancer Research. 1996 ; Vol. 56, No. 4. pp. 706-709.
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