Effect of intratympanic dexamethasone administration on cispaltin-induced ototoxicity in adult guinea pigs, is it time-dependent? Audiological and histological study

Abstract

Introduction: Cisplatin is a cornerstone chemotherapeutic drug often dose-limited by ototoxicity. Many trials have been introduced for a complete cure or prevention of cisplatin-induced ototoxicity but unfortunately, with un-satisfactory results. Intratympanic steroids have been recently tried and shown competitive results in terms of reduction of ototoxicity. However, perfect timing of drug administration remains controversial. Aim of the work: To evaluate the effect and safety of intratympanic dexamethasone administration on cisplatininduced ototoxicity in adult male guinea pigs and to assess the differences between early and late protection from this ototoxicity. Materials and methods: Forty eight adult male guinea pigs were divided as follows: Group I served as control group. Group II was subjected to intratympanic saline (subgroup IIa) or dexamethasone (subgroup IIb) injection. Group III was intraperitoneally injected with cisplatin. Groups IV and V were subjected first to intratympanic dexamethasone administration in both ears for 5 days starting 1 day and 1 hour -respectively- before cisplatin intraperitoneal injection. Results: Dexamethasone intratympanic injection revealed similar functional and structural results compared with control. Cisplatin intraperitoneal injection resulted in a profound cochlear functional and structural damage in group III. Limited otoprotection resulted from intratympanic dexamethasone administration one day before cisplatin. Intratympanic dexamethasone injection one hour before cisplatin treatment resulted in a significant preservation of the functional and structural properties of the cochlea. Conclusion: Intratympanic dexamethasone administration is a safe, easy and efficient way to protect from cisplatin ototoxicity especially when administered one hour before cisplatin treatment.