Local administration of antioxidants to the inner ear: Kinetics and distribution
- 作者：Laurell ; G. ; Teixeira ; M. ; Sterkers ; O. ; Bagger-Sjö ; bä ; ck ; D. ; Eksborg ; S. ; Lidman ; O. ; et. al.
- 关键词：Pharmacokinetics ; Autoradiography ; Scavenger ; Scala tympani perilymph ; Lateral wall ; PLT ; scala tympani perilymph ; ROS ; reactive oxygen species ; r.w. ; round window
- 刊名：Hearing Research
- 出版年：2002
- 期刊代码：111_03785955
- 类别：med
- 出版时间：November, 2002
- 卷：173
- 期：1-2
- 页码：198-209
- 文件大小：900 K
摘要
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.