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Cisplatin-induced metabolome changes in serum: an experimental approach to identify markers for ototoxicity
Pernilla Videhult Pierre1,2, Jakob Haglöf3, Birgitta Linder1
1a Department of Surgical Sciences , Uppsala University, Uppsala University Hospital, ENT Clinic , Uppsala , Sweden.
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.
