在动物模型中，d-蛋氨酸可降低妥布霉素诱导的耳毒性，且无抗菌干扰作用。
d-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models.
作者信息
Fox Daniel J, Cooper Morris D, Speil Cristian A, Roberts Melissa H, Yanik Susan C, Meech Robert P, Hargrove Tim L, Verhulst Steven J, Rybak Leonard P, Campbell Kathleen C M
机构信息
Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA; Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA; Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA.
Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA.
出版信息
J Cyst Fibros. 2016 Jul;15(4):518-30. doi: 10.1016/j.jcf.2015.06.005. Epub 2015 Jul 10.
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 20kHz in the 420mg/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.
背景
妥布霉素是治疗囊性纤维化的关键药物，但其会导致耳毒性。本研究测试了d - 蛋氨酸对妥布霉素诱导的耳毒性的保护作用以及潜在的抗菌干扰。
方法
通过听觉脑干反应（ABR）和外毛细胞（OHC）定量分析，检测用妥布霉素和一系列d - 蛋氨酸剂量处理的豚鼠的保护情况。体外抗菌干扰研究测试了抑制作用和抗生素后效应分析。体内抗菌干扰研究测试了正常和中性粒细胞减少的大肠杆菌小鼠的存活率以及腹腔灌洗细菌计数。
结果
d - 蛋氨酸使ABR阈值偏移显著降低。在420mg/kg/天的组中，OHC保护作用虽不那么显著，但在20kHz时具有显著性。体外研究未检测到d - 蛋氨酸诱导的抗菌干扰。体内研究未在正常或中性粒细胞减少的小鼠中检测到d - 蛋氨酸诱导的干扰。
结论
d - 蛋氨酸可预防妥布霉素诱导的耳毒性，且无抗菌干扰。研究结果表明d - 蛋氨酸可作为囊性纤维化患者临床使用妥布霉素时的潜在耳保护剂。
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