Delayed, Reversible Hearing Loss Caused by Difluoromethylornithine (DFMO)

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Abstract
Objectives/Hypothesis Difluoromethylornithine (DFMO) is an anticancer experimental drug that is ototoxic. The objectives of these three experiments were to: 1) determine a dose and dosing schedule of DFMO that produces significant hearing loss (HL) in newborn gerbils; 2) compare the HL level for control and newborn gerbils receiving daily subcutaneous injections of DFMO; and 3) to determine if DFMO‐related HL is significantly reversible following discontinuation of DFMO treatment.Study Design Prospective, non‐randomized experimental design with placebo controls.Methods Click‐evoked auditory brainstem response (ABR) testing was performed for 21‐day‐old Mongolian gerbils following daily subcutaneous injections of DFMO or saline. Three experiments were carried out using different injection schedules and doses of DFMO. In experiment 3, animals were retested at 42 days of age following a 3‐week recovery from DFMO.Results Animals administered an 18‐day regimen of DFMO at 1 g/kg per day (from day 3 to day 20) had click thresholds of 25 to 65 dB nHL, whereas animals receiving daily injections of saline had thresholds of 5 to 20 dB nHL. Animals retested after 3 weeks of recovery from DFMO treatment had thresholds ranging from 5 to 20 dB nHL. Differences were statistically significant.Conclusions DFMO causes mild to moderate HL in neonatal gerbils that recovers after discontinuation of the drug.