Distribution of gentamicin in the guinea pig inner ear after local or systemic application
Distribution of gentamicin in the guinea pig inner ear after local or systemic application
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DOI：
10.1007/s10162-002-2036-8
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发表时间：
2003-06-01
影响因子：
2.4
通讯作者：
Adams, JC
中科院分区：
文献类型：
--
作者：
Imamura, S;Adams, JC
采用免疫细胞化学方法定位药物，观察单次腹腔注射或圆形窗口局部应用庆大霉素后，豚鼠内耳细胞对庆大霉素的摄取和保留情况。两种情况下积聚药物的细胞相同，但药物染色更强烈，局部应用后常伴有广泛的耳蜗变性。两种给药方式给药后不久，迷宫内包括骨在内的所有组织均可见弥漫性染色。后来，当不同的细胞染色变得明显时，几乎所有的细胞类型都呈阳性，有几种细胞类型的染色比毛细胞更暗，这表明毛细胞不是最热衷于积累庆大霉素的。在几乎所有病例中，听神经毛细胞和前庭毛细胞的针下部分以及螺旋韧带的III型纤维细胞均呈阳性染色，这些部位在给药后长达6个月的时间内均呈阳性。在丧失Corti器官的动物中，螺旋韧带根细胞、血管纹边缘细胞和螺旋边缘细胞的庆大霉素染色异常强烈。在明显组织破坏的情况下，幸存细胞的深色染色表明，药物引起的损伤程度的变化更多地取决于局部吸收的程度，而不是动物全身代谢药物能力的差异。目前的结果表明庆大霉素在单次圆窗应用后可能损伤或破坏所有耳蜗细胞。这些发现拓宽了我们对耳蜗庆大霉素摄取和损害的认识范围，并对通过向中耳输入氨基糖苷类药物治疗前庭疾病患者以及氨基糖苷类药物导致耳聋的患者的康复前景具有指导意义。
Uptake and retention of gentamicin by cells in the guinea pig inner ear after a single peritoneal injection or local application on the round window were investigated using immunocytochemistry to localize the drug. The cells that accumulated the drug under the two conditions were the same, but staining for the drug was more intense and was often accompanied by widespread cochlear degeneration following local application. Soon after drug administration by either route, there was diffuse staining for the drug throughout all tissue within the labyrinth, including bone. At later times when distinct cell staining became evident, virtually all cell types were found to be positive, with several cell types staining more darkly for the drug than hair cells, indicating that hair cells were not the most avid in accumulating gentamicin. The infracuticular portion of auditory and vestibular hair cells as well as type III fibrocytes of the spiral ligament were positively stained in almost all cases and these sites were found to be positive for as long as six months post administration. In animals with loss of the organ of Corti, there was unusually intense staining for gentamicin in root cells of the spiral ligament, in marginal cells of the stria vascularis, and in cells of the spiral limbus. Dark staining of surviving cells in cases with overt tissue destruction suggests that variability in the extent of damage caused by the drug was determined more by the degree of its local uptake than by differences in animals' capacities to metabolize the drug systemically. The present results show that gentamicin may damage or destroy all cochlear cells following a single round window application. The findings broaden the scope of our knowledge of cochlear gentamicin uptake and damage and have implications for treatment of patients with vestibular disorders by infusion of aminoglycosides into the middle ear, as well as implications for prospects of rehabilitating patients that have been deafened by aminoglycosides.