title: Is intratympanic injection of erdosteine protective against cisplatin-induced ototoxicity?
abstract: Cisplatin induces ototoxicity in adult and pediatric population. Our aim was (1) to assess the protective effect of intratympanic injections of erdosteine in the prevention of cisplatin-induced ototoxicity and (2) to investigate inner ear protection using a scanning electron microscope. Ears of 20 Hartley guinea pigs were assigned to four subgroups and received an intratympanic injection of: E1-erdosteine 1.125 mg/cc, NS-normal saline, E2-erdosteine 2.25 mg/cc and E4-erdosteine 4.5 mg/cc. After 45 min, an intraperitoneal cisplatin injection of 3 mg/kg was performed and repeated 8 times, once a week to achieve 24 mg/kg. Auditory brainstem responses were recorded before any injection and after 24 mg/kg of cisplatin for the frequencies 1, 2, 4, 6 and 8 kHz. Cochleas were analyzed under scanning electron microscope. Average hearing loss in the NS subgroup was 29.8 dB which was lower than E1, E2 and E4 subgroups (40, 43.9, and 51.7 dB, respectively). Difference in the mean threshold increase was statistically significant between NS and the three erdosteine subgroups (P < 0.03). No difference was identified between E1 and E2 (P > 0.05). However, difference was significant between E1 and E4 (P < 0.02) and between E2 and E4 (P < 0.03); Electron microscopy revealed almost complete destruction of the stereocilia of the outer hair cells in all subgroups (NS, E1, E2 and E4). The ears treated with erdosteine showed a diffuse inflammatory reaction and osteitis of the middle ear. Low or high concentration of intratympanic erdosteine does not offer protection against cisplatin-induced ototoxicity as it causes a considerable inflammatory reaction.
authors: Department of Otolaryngology Head and Neck Surgery, Sainte-Justine University Hospital Center (CHU SJ), Montreal University, 3175, Côte Sainte-Catherine, Montreal, QC H3T 1C5, Canada. issam.saliba@umontreal.ca
authors: Issam
authors: I
authors: Saliba
authors: Fouad
authors: F
authors: El Fata
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D001309:Auditory Threshold / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005100:Expectorants / Q000494:pharmacology; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D034381:Hearing Loss / Q000139:chemically induced* / Q000517:prevention & control*; D007267:Injections / Q000379:methods; D008855:Microscopy, Electron, Scanning; D018696:Neuroprotective Agents / Q000494:pharmacology; D012405:Round Window, Ear; D013864:Thioglycolates / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D017211:Treatment Failure; D014432:Tympanic Membrane
chemical_list: D000970:Antineoplastic Agents; D005100:Expectorants; D018696:Neuroprotective Agents; D013864:Thioglycolates; D013876:Thiophenes; C048498:erdosteine; D002945:Cisplatin