In vitro and animal studies of sodium thiosulfate as a potential chemoprotectant against carboplatin-induced ototoxicity.
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.
Neuwelt
E A
EA
Department of Neurology, Oregon Health Sciences University, Portland 97201 USA.
Brummett
R E
RE
Remsen
L G
LG
Kroll
R A
RA
Pagel
M A
MA
McCormick
C I
CI
Guitjens
S
S
Muldoon
L L
LL
D000161:Acoustic Stimulation; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D016190:Carboplatin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018288:Carcinoma, Small Cell; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013885:Thiosulfates / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D013885:Thiosulfates; D005665:Furosemide; D016190:Carboplatin; C017717:sodium thiosulfate