Aran J M, Dulon D, Hiel H, Erre J P, Aurousseau C
Laboratoire d'Audiologie Expérimentale, INSERM U229, Université Bordeaux II, Hôpital Pellegrin, France.
Rev Laryngol Otol Rhinol (Bord). 1993;114(2):125-8.
Recent experiments using autoradiographic and immunohistochemical labelling of gentamicin have demonstrated that GM penetrates specifically into the sensory cells of the inner ear, with a good correlation between the intensity of the labelling and the respective degrees and localisations of ototoxic damages. In the sensory hair cells GM ils localised below the cuticular plate, in an area rich in lysosomes during the ototoxic treatment. This penetration precedes the development of ototoxicity and there seems to be a threshold of intracellular concentration of GM for development of intracellular ototoxic processes. Clearance is very slow since GM can still be observed 11 months after the end of a non toxic treatment (60 mg/kg/day for 6 consecutive days). This observation is of clinical interest, in view of the delayed development of ototoxicity often observed clinically, and with respect to other hazards, including new ototoxic treatments, to which the cells can be exposed while loaded with the aminoglycoside molecule.
最近利用庆大霉素放射自显影和免疫组织化学标记的实验表明,庆大霉素可特异性地渗透到内耳的感觉细胞中,标记强度与耳毒性损害的程度及部位之间具有良好的相关性。在耳毒性治疗期间,庆大霉素在内耳感觉毛细胞中位于角质板下方富含溶酶体的区域。这种渗透在耳毒性发生之前,并且似乎存在庆大霉素细胞内浓度阈值,超过该阈值会引发细胞内耳毒性过程。清除非常缓慢,因为在无毒治疗(连续6天每天60mg/kg)结束11个月后仍可观察到庆大霉素。鉴于临床上经常观察到耳毒性的延迟发生,以及考虑到细胞在负载氨基糖苷分子时可能暴露于其他危害(包括新的耳毒性治疗),这一观察结果具有临床意义。