D-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models
D-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models
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DOI：
10.1016/j.jcf.2015.06.005
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发表时间：
2016-07-01
影响因子：
5.2
通讯作者：
Campbell, Kathleen C. M.
中科院分区：
文献类型：
--
作者：
Fox, Daniel J.;Cooper, Morris D.;Campbell, Kathleen C. M.
背景：妥布霉素是一种重要的囊性纤维化治疗药物，但会引起耳毒性。本研究测试D-甲硫氨酸保护妥布霉素诱导的耳毒性和潜在的抗菌interference.Methods：听觉脑干反应（ABR）和外毛细胞（OHC）的定量测量与妥布霉素和一系列的D-甲硫氨酸剂量治疗的豚鼠的保护。体外抗菌干扰研究检测了抑制和抗生素后效应试验。在体内抗微生物干扰的研究测试正常和血小板减少大肠杆菌小鼠的生存和腹腔灌洗bacterial counts.Results：D-Methylamine赋予显着的ABR阈值偏移降低。在420 mg/kg/天剂量组中，OHC保护不太稳健，但在20 kHz下显著。体外研究未检测到D-蛋氨酸诱导的抗菌干扰。在体内研究没有检测到D-蛋氨酸诱导的干扰正常或血小板减少mice.Conclusions：D-蛋氨酸保护妥布霉素诱导的耳毒性无抗菌干扰。研究结果表明，D-met作为一种潜在的耳保护剂，可用于囊性纤维化患者的临床妥布霉素使用。由Elsevier B. V.代表欧洲囊性纤维化协会出版。
Background: Tobramycin is a critical cystic fibrosis treatment however it causes ototoxicity. This study tested D-methionine protection from tobramycin-induced ototoxicity and potential antimicrobial interference.Methods: Auditory brainstem responses (ABRs) and outer hair cell (OHC) quantifications measured protection in guinea pigs treated with tobramycin and a range of D-methionine doses. In vitro antimicrobial interference studies tested inhibition and post antibiotic effect assays. In vivo antimicrobial interference studies tested normal and neutropenic Escherichia coli murine survival and intraperitoneal lavage bacterial counts.Results: D-Methionine conferred significant ABR threshold shift reductions. OHC protection was less robust but significant at 20 kHz in the 420 mg/kg/day group. In vitro studies did not detect D-methionine-induced antimicrobial interference. In vivo studies did not detect D-methionine-induced interference in normal or neutropenic mice.Conclusions: D-Methionine protects from tobramycin-induced ototoxicity without antimicrobial interference. The study results suggest D-met as a potential otoprotectant from clinical tobramycin use in cystic fibrosis patients. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.