Videhult Pierre Pernilla, Haglöf Jakob, Linder Birgitta, Engskog Mikael K R, Arvidsson Torbjörn, Pettersson Curt, Fransson Anette, Laurell Göran
a Department of Surgical Sciences , Uppsala University, Uppsala University Hospital, ENT Clinic , Uppsala , Sweden.
b Department of Clinical Science, Intervention, and Technology, Division of Audiology , Karolinska Institutet , Huddinge , Sweden.
Acta Otolaryngol. 2017 Oct;137(10):1024-1030. doi: 10.1080/00016489.2017.1325006. Epub 2017 May 24.
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.
To investigate cisplatin-induced change of the serum metabolite profile and its association with ototoxicity.
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.
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.
抗癌药物顺铂治疗引起的耳毒性仍是一个临床问题。在体内已发现顺铂有广泛的细胞内靶点。
研究顺铂诱导的血清代谢物谱变化及其与耳毒性的关系。
豚鼠（n = 14）在给予耳保护剂候选物硫代硫酸钠（STS组；n = 7）或氯化钠（NaCl组；n = 7）30分钟后静脉注射顺铂（8 mg/kg体重）。在药物治疗前和治疗后4天通过听性脑干反应（ABR，3 - 30 kHz）以及评估毛细胞损失来评估耳毒性。在药物治疗前和治疗后4天采集血样，使用液相色谱 - 质谱联用仪分析血清中的极性代谢组。
顺铂治疗导致两组的阈值显著升高和外毛细胞（OHC）损失。STS组的耳毒性通常较低，但仅在30 kHz时达到显著差异（p = 0.007）。顺铂治疗使两组的代谢物谱发生显著且相似的改变。在NaCl组中，发现L - 乙酰肉碱、N - 乙酰神经氨酸、神经酰胺和半胱氨酰丝氨酸与高频听力损失之间存在显著的负相关。这些相关性的意义应在针对性研究中进行探索。
