title: The impact of erdosteine on cisplatin-induced ototoxicity: a proteomics approach.
abstract: Cisplatin is a commonly used chemotherapeutic agent and causes serious side effects, including progressive and irreversible hearing loss. No treatment is currently available for cisplatin-induced ototoxicity. We have previously demonstrated that erdosteine, a potent antioxidant, partially protected the cochlea against cisplatin toxicity in vivo. The aims of this study were to (1) evaluate the protein profiles of the cochlea following cisplatin administration and (2) evaluate the impact of erdosteine on the protein profile using a proteomics-based approach. Thirty Sprague-Dawley rats were injected intraperitoneally with saline (n = 10), cisplatin (n = 10) or with cisplatin and erdosteine (n = 10). The cisplatin dosage was 14 mg/kg and for erdosteine, 500 mg/kg. Following euthanasia, protein lysates were obtained from fresh-frozen cochleae and were processed for mass spectrometry and western blotting. We detected 445 proteins that exhibited a twofold change or greater in the cisplatin group as compared to the control group. Of these, 18 proteins showed a fourfold or greater change in expression associated with cisplatin administration, including ras-related protein Rab-2A, Rab-6A, cd81, ribosomal protein S5, and myelin basic protein, which were downregulated, while Ba1-647 and fibrinogen (alpha chain), amongst others, were upregulated. Co-administration of erdosteine revealed a reversal of these changes in the expression of ras-related protein Rab-2A, ribosomal protein S5, myelin basic protein, and fibrinogen (alpha chain); erdosteine also upregulated glutathione reductase. In this study, we identified various proteins that may play a role in cisplatin-induced ototoxicity. We also observed the changes resulting from co-treatment with an antioxidant.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Montreal Children's Hospital, McGill University, 1001 Boulevard Décarie, Montreal, QC, H4A 3J1, Canada. sofia.waissbluth@gmail.com.
authors.forename: Sofia
authors.initials: S
authors.lastname: Waissbluth
authors.affiliation: Montreal Children's Hospital Research Institute, Montreal, QC, Canada.
authors.forename: Delphine
authors.initials: D
authors.lastname: Garnier
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Montreal Children's Hospital, McGill University, 1001 Boulevard Décarie, Montreal, QC, H4A 3J1, Canada.
authors.forename: Olubunmi V
authors.initials: OV
authors.lastname: Akinpelu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Montreal Children's Hospital, McGill University, 1001 Boulevard Décarie, Montreal, QC, H4A 3J1, Canada.
authors.forename: Pezhman
authors.initials: P
authors.lastname: Salehi
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Montreal Children's Hospital, McGill University, 1001 Boulevard Décarie, Montreal, QC, H4A 3J1, Canada.
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Daniel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D016022:Case-Control Studies; D002945:Cisplatin / Q000009:adverse effects*; D003051:Cochlea / Q000378:metabolism*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000517:prevention & control; D013058:Mass Spectrometry; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics; D017207:Rats, Sprague-Dawley; D013864:Thioglycolates / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D011506:Proteins; D013864:Thioglycolates; D013876:Thiophenes; C048498:erdosteine; D002945:Cisplatin
keywords: Cisplatin; Erdosteine; Ototoxicity; Platinum; Protein; Proteomics