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Cisplatin-induced metabolome changes in serum: an experimental approach to identify markers for ototoxicity
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Karolinska Inst, Div Audiol, Dept Clin Sci Intervent & Technol, Alfred Nobels Alle 10 Plan 5, SE-14183 Huddinge, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.ORCID iD: 0000-0001-8650-6245
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
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2017 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, no 10, p. 1024-1030Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Ototoxicity from treatment with the anticancer drug cisplatin remains a clinical problem. A wide range of intracellular targets of cisplatin has been found in vivo.

AIM: To investigate cisplatin-induced change of the serum metabolite profile and its association with ototoxicity.

MATERIAL AND METHODS: Guinea pigs (n = 14) were treated with cisplatin (8 mg/kg b.w., i.v.) 30 min after administration of the otoprotector candidate sodium thiosulfate (group STS; n = 7) or sodium chloride (group NaCl; n = 7). Ototoxicity was evaluated by ABR (3-30 kHz) before and 4 d after drug treatment, and by assessment of hair cell loss. A blood sample was drawn before and 4 d after drug treatment and the polar metabolome in serum was analyzed using LC-MS.

RESULTS: Cisplatin-treatment caused significant threshold elevations and outer hair cell (OHC) loss in both groups. The ototoxicity was generally lower in group STS, but a significant difference was reached only at 30 kHz (p = .007). Cisplatin treatment altered the metabolite profile significantly and similarly in both groups. A significant inverse correlation was found between L-acetylcarnitine, N-acetylneuraminic acid, ceramide, and cysteinylserine and high frequency hearing loss in group NaCl. The implication of these correlations should be explored in targeted studies.

Place, publisher, year, edition, pages
2017. Vol. 137, no 10, p. 1024-1030
Keywords [en]
ABR, cisplatin, hair cell, metabolite profiling, ototoxicity, sodium thiosulfate
National Category
Basic Medicine Analytical Chemistry Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-328151DOI: 10.1080/00016489.2017.1325006ISI: 000407072000002PubMedID: 28537102OAI: oai:DiVA.org:uu-328151DiVA, id: diva2:1134232
Funder
AFA InsuranceAvailable from: 2017-08-18 Created: 2017-08-18 Last updated: 2018-09-07Bibliographically approved

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Pierre, Pernilla VidehultHaglöf, JakobLinder, BirgittaEngskog, Mikael K RArvidsson, TorbjörnPettersson, CurtFransson, Anette ELaurell, Göran

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Otolaryngology and Head and Neck SurgeryAnalytical Pharmaceutical Chemistry
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