Cisplatin ototoxicity and otoprotection with sodium salicylate.
Cisplatin is a potent antineoplastic drug widely used for the treatment of cancer in both adults and children. One of its most important side effects is ototoxicity, which leads to irreversible bilateral hearing loss for high frequencies (4-8 kHz). Several studies have tried to identify drugs that, when combined with cisplatin, may act as otoprotectors. The mechanism of ototoxicity of cisplatin is known to be related to changes in the antioxidant mechanisms of hair cells, especially the outer hair cells of the cochlea. Our proposal was to assess the action of sodium salicylate, which has a known antioxidant property, as a possible otoprotector of outer hair cells against the action of cisplatin, using distortion product otoacoustic emissions (DPOAEs) and scanning electron microscopy. The study was conducted on albino guinea pigs divided into two groups: group 1 (n = 9, 18 cochleae) receiving a cisplatin dose of 8.0 mg/kg/day by the intraperitoneal (ip) route for 3 days, group 2 (n = 10, 20 cochleae) receiving 100 mg/kg sodium salicylate by the subcutaneous route followed 90 min later by cisplatin, 8.0 mg/kg/day ip for 3 days, and group 3 (n = 3, six cochleae) treated with 100 mg/kg day sodium salicylate for 3 days. In group 1, there was damage with the absence of cilia in all three rows of outer hair cells in the basal turn, followed by turns 2 and 3. In group 2, hair cells were present in all cochlear turns, but exhibited disarrangement of the ciliary structure, especially in row 1, and the DPOAEs were absent after 3 days of treatment. We conclude that drugs such as sodium salicylate, because of their antioxidant properties, may protect, at least partially, the outer hair cells against cisplatin ototoxicity.
Hyppolito
Miguel Angelo
MA
Division of Otorhinolaryngology, Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil. mhyppolito@uol.com.br
de Oliveira
José Antonio A
JA
Rossato
Maria
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D001309:Auditory Threshold / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects / Q000648:ultrastructure; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D008855:Microscopy, Electron, Scanning; D017084:Otoacoustic Emissions, Spontaneous / Q000502:physiology; D012980:Sodium Salicylate / Q000627:therapeutic use*; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D002945:Cisplatin; D012980:Sodium Salicylate