Is Intratympanic Injection of Erdosteine Protective Against Cisplatin-Induced Ototoxicity?

• Published in: Neurotoxicity research Vol. 21; no. 3; pp. 302 - 308
• Main Authors: Saliba, Issam, El Fata, Fouad
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01-04-2012
• Subjects: Animals; Antineoplastic Agents - toxicity; Auditory Threshold - drug effects; Biomedical and Life Sciences; Biomedicine; Brain stem; Cell Biology; Cisplatin; Cisplatin - toxicity; Cochlea; Electron microscopy; Evoked Potentials, Auditory, Brain Stem - drug effects; Expectorants - pharmacology; Guinea Pigs; Hair Cells, Auditory, Outer - drug effects; Hair Cells, Auditory, Outer - pathology; Hair Cells, Auditory, Outer - ultrastructure; Hearing loss; Hearing Loss - chemically induced; Hearing Loss - prevention & control; Inflammation; Injections - methods; Inner ear; Microscopy, Electron, Scanning; Middle ear; Neurobiology; Neurochemistry; Neurology; Neuroprotective Agents - pharmacology; Neurosciences; Neurotoxicity; Osteitis; Ototoxicity; outer hair cells; Pediatrics; Pharmacology/Toxicology; Round Window, Ear; Scanning electron microscopy; Statistical analysis; Thioglycolates - pharmacology; Thiophenes - pharmacology; Treatment Failure; Tympanic Membrane; Erdosteine; Round window; Cisplatin; Inner ear; Outer hair cell; Ototoxicity
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/s12640-011-9282-7

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.