Experimental Drug MnTBAP Shows Promise in Preventing Cisplatin-Induced Hearing Loss in Mice
A preclinical study found that MnTBAP, a superoxide dismutase mimetic, prevented cisplatin-induced hearing loss and cochlear cell damage in mice. Cisplatin is a widely used chemotherapy drug whose ototoxicity has no broadly approved preventive treatment, with sodium thiosulfate approved only for pediatric use. The findings suggest MnTBAP could be a candidate therapeutic to protect hearing in cancer patients undergoing cisplatin chemotherapy.
Researchers tested MnTBAP, a manganese-based antioxidant compound, as a potential otoprotective agent in CBA/J mice treated with cisplatin at 3 mg/kg daily for five days. Cisplatin treatment elevated nitrotyrosine levels—a marker of oxidative and nitrosative stress—in cochlear hair cells and spiral ganglion neurons (SGNs), and caused significant loss of these cells in the middle and basal regions of the cochlea. Functional hearing assessments via auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) confirmed elevated hearing thresholds and reduced DPOAE amplitudes following cisplatin exposure. Co-treatment with MnTBAP at 10 mg/kg daily for eight days prevented these functional and morphological changes, preserving both hair cells and SGN density. A negative correlation was observed between nitrotyrosine levels and surviving cell counts, implicating oxidative stress as a key mechanism of cisplatin ototoxicity. The authors conclude that MnTBAP warrants further investigation as a clinical candidate to protect hearing in patients receiving cisplatin-based chemotherapy.
What's missing
As a preprint mouse study, key limitations include: no pharmacokinetic or safety data for MnTBAP in humans, no assessment of whether MnTBAP interferes with cisplatin's antitumor efficacy (a critical concern for any otoprotective agent), no dose-response optimization, and no long-term follow-up data. The study has not yet undergone peer review.
What different sources said
- bioRxivCenter
Otoprotective effect of MnTBAP in cisplatin-induced hearing loss
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