Journal
LARYNGOSCOPE
Volume 116, Issue 2, Pages 292-296Publisher
WILEY
DOI: 10.1097/01.mlg.0000197630.85208.36
Keywords
cisplatin; HL; histone deacetylase inhibitors; sodium butyrate; otoprotection
Funding
- NIDCD NIH HHS [F31 DC000152, P30 DC05209, KO8 DC00152, R01 DC000152, R01 DC0188, P30 DC005209, R01 DC000188] Funding Source: Medline
- NINDS NIH HHS [R01 NS040591, R01 NS040591-04] Funding Source: Medline
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There is a need for otoprotective agents that can be administered systemically without compromising cancer treatment. Histone deacetylase inhibitors are anticancer agents that act by upregulating the expression of cell-cycle control genes. They are also neuroprotective, leading us to hypothesize that they might be otoprotective. The goal of this study was to determine if the antitumor agent sodium butyrate (a histone deacetylase inhibitor) protects against cisplatin ototoxicity when administered systemically. Study Design: This was an animal study. Methods: Cisplatin was administered to guinea pigs who received either 12 days of sodium butyrate (7 d before and 5 d after cisplatin) or equivolume saline injections. Hearing was tested with distortion product otoacoustic emission (DPOAE) analysis before the start of the study and 2 weeks after cisplatin treatment. Results: Guinea pigs given a single intraperitoneal injection of 14 mg/kg cisplatin experience a mean hearing loss of 8 dB across the frequencies of 3.5, 5, 7, 10, 14, and 20 kHz. Intraperitoneal injection of 1.2 mg/kg sodium butyrate per day for 7 days before and 5 days after cisplatin almost completely eliminates this threshold shift (P = .0011). Conclusions: The histone deacetylase inhibitor sodium butyrate gives almost complete protection in a single-dose model of cisplatin ototoxicity in guinea pigs. Because histone deacetylase inhibitors are anticancer agents with very few side effects, they may be candidates for clinical use during cisplatin chemotherapy.
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