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effect of sodium thiosulfate

A number of agents have been investigated in animal models as otoprotection against the toxic effects of cis- and carboplatin. Among these, sodium thiosulfate (STS) has shown particular promise as an otoprotective agent. STS is approved by the US Food and Drug Administration (FDA) as an antidote for cyanide and nitroprusside toxicity and for calciphylaxis. STS has been shown to act as both an antioxidant as well as a chelating agent in vivo. The chelating properties of the sulfur-thiol functional group are believed to be responsible for the otoprotective effects of STS, binding to, and inactivating the platinum. The thiol compound may also act to scavenge reactive oxygen species produced by the platinum, thus preventing the initiation of the apoptotic pathway.

Several studies have demonstrated the otoprotective effects of intravenous STS in animal models. Subsequent studies have shown similar benefit when STS is administered intravenously to humans. A major drawback to this mode of delivery, however, is the fear that it reduces the anti-tumor activity of the platinum. Sodium thiosulfate is believed to bind to cisplatin, forming a complex that is then excreted by the kidneys. Though this may decrease the ototoxicity associated with the platinum, it may also decrease the anti-neoplastic properties of the agent. There are conflicting reports of reduced tumoricidal properties of STS in vitro, though there are no in vivo studies suggesting this adverse effect in vivo.

In view of the potential for systemic STS to reduce the tumoricidal effects of platinum agents, researchers have sought an alternate mode of delivery. Recent animal studies have examined the effect of sodium thiosulfate delivered locally to the middle ear space. Stocks, et al demonstrated an otoprotective effect of STS delivered to the middle ear space of guinea pigs. Wang, et al showed complete prevention of the ototoxic effects of cisplatin in guinea pigs treated with round window application of STS. In their study, both the compound action potential (CAP) and distortion product otoacoustic emissions (DPOAE) were unchanged, and both outer hair cells (OHC) and inner hair cells (IHC) were preserved. This effect, however, was not demonstrated in a similar study by Wimmer, et al. The temporal and spatial separation of the platinum and STS in these animal studies prompted Zuur and colleagues to state that, “in the future, it may be desirable to examine additional possibilities for two-route administration schemes for chemotherapy and otoprotective drugs in humans.” There are no studies to date of intratympanic sodium thiosulfate in humans.