Impact of pH on Intratympanic Sodium Thiosulfate-hyaluronan Gel in Preventing Cisplatin-induced Ototoxicity

Hypothesis: The pH of an intratympanic gel influences the level of protection against the ototoxic effects of systemic cisplatin. Background: Nucleophiles reduce cisplatin-induced ototoxicity by chemically inactivating cisplatin and counteracting oxidative stress. pH is a factor influencing cisplatin's reactivity. Here, intratympanic administration of a hyaluronan-based gel containing the nucleophile sodium thiosulfate (STS) was used to investigate the role of pH in otoprotection. Methods: Guinea pigs (n=32) received a unilateral transtympanic injection of a hyaluronan-based gel (0.10 to 0.15 mL) with either STS at pH 6.5 or pH 8.0, or NaCl at pH 6.5 or pH 8.0. The contralateral ear served as control. After 30 minutes, cisplatin (8 mg/kg b.w., i.v.) was administered. Cochleae were harvested 4 days later for hair cell quantification. Results: Mean percentage of outer hair cell (OHC) loss per mm in the region ≤10 mm from the round window had a median absolute intraindividual difference of 6.0% (quartiles 1 and 2: 3.8% to 11%; P =0.012; n=8) in group STS pH 6.5 and 5.8% (1.8% to 18%; P =0.046; n=6) in group STS pH 8.0, favoring the gel-treated ear. The corresponding numbers in the NaCl groups were -0.2% (-2.2 to 8.7%; P =1.000; n=8) in group NaCl pH 6.5 and 3.3% (-8.1% to 22%; P =0.237; n=7) in group NaCl pH 8.0. The difference between nontreated and gel-treated ears did not differ significantly between the 2 STS groups. Conclusion: STS in a hyaluronan-based gel reduced OHC loss equally well at both pH levels, while NaCl was ineffective.