Local administration of antioxidants to the inner ear -: Kinetics and distribution

Local administration of antioxidants to the inner ear -: Kinetics and distribution
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DOI:
10.1016/s0378-5955(02)00613-5
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发表时间:
2002-11-01
期刊:
影响因子:
2.8
通讯作者:
Ferrary, E
Ferrary, E
中科院分区:
医学1区
文献类型:
--
作者:
Laurell, G;Teixeira, M;Ferrary, E

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圆窗(r.w.)药物的给药包括通过R.W.将药物直接输送到内耳。膜,避免治疗的全身效应。早期的实验研究表明,一些抗氧化剂和清除剂有望改善某些后天性耳蜗疾病中活性氧的组织损伤能力。甲硫氨酸和硫脲是两种含硫小分子,具有抗氧化和清除作用。穿过r.w.的通道。放射性D-蛋氨酸和硫脲通过1小时输注到r.w.在大鼠模型中进行了研究。在r.w.后17-254分钟测量鼓阶外淋巴液(PLT)中示踪剂的水平。局两个示踪剂都通过了r. w。膜容易。在给药后最早采集的样本中发现了峰值水平。基底回PLT中的放射性达到峰值,约为冲洗介质放射性的1.5-1.9%。在R.W.之后给药后,放射性D-蛋氨酸和硫脲的浓度下降,终末半衰期分别为0.57和0.77 h。通过放射自显影术分析示踪剂在细胞水平上的分布。耳蜗外侧壁表达最强。可以推测,D-蛋氨酸和硫脲通过r.w.在基底回中PLT中的物质局部浓度较高。(C)2002 Elsevier Science B. V.保留所有权利。
Round window (r.w.) administration of drugs involves the delivery of medication directly into the inner ear via the r.w. membrane, avoiding a systemic effect of the therapy. Earlier experimental studies suggest that a number of antioxidants and scavengers hold promise for ameliorating the tissue damaging capacity of reactive oxygen species in some acquired cochlear disorders. D-Methionine and thiourea are two small sulfur-containing molecules with an antioxidative and scavenging effect. The passage through the r.w. of radioactive D-methionine and thiourea administered by 1 h infusion to the r.w. was studied in a rat model. Levels of the tracers were measured in scala tympani perilymph (PLT) 17-254 min after r.w. administration. Both tracers pass the r.w. membrane readily. Peak levels were found in the earliest taken samples after the administration. The radioactivity in PLT of the basal turn reached a peak to about 1.5-1.9% of the irrigating medium radioactivity. Following the r.w. administration, the concentration of radioactive D-methionine and thiourea declined with a terminal half-life of 0.57 and 0.77 h, respectively. The distribution of the tracers at the cellular level was analyzed by autoradiography. The most intense expression was found in the lateral wall of the cochlea. It can be postulated that local delivery to the cochlea Of D-methionine and thiourea via the r.w. gives high local concentrations of the substances in PLT in the basal turn. (C) 2002 Elsevier Science B.V. All rights reserved.