Kawasaki H, Yamada Y, Takei T, Akiyoshi M
Jpn J Antibiot. 1982 Jun;35(6):1553-61.
The ototoxicity of netilmicin (NTL) in pregnant guinea pigs (Hartley strain) and the newborn was examined and compared to that of gentamicin (GM). NTL was administered intramuscularly at dose of 90 mg/kg to pregnant guinea pigs from day 0 to day 35 of pregnancy (the early period of pregnancy) or from day 42 of pregnancy to 1 day prior to delivery (the late period of pregnancy). GM at dose of 45 mg/kg or physiological saline were administered intramuscularly to pregnant guinea pigs during the late period of pregnancy. Four of 5 dams given NTL during the early period of pregnancy, 4 of 7 dams given TNL during the late period of pregnancy, and 2 of 4 dams given GM during the late period of pregnancy died. No pinna reflex loss in frequency range from 2 to 20 KHz were detected in mother guinea pigs treated with NTL either during the early period of pregnancy or during the late period of pregnancy. GM caused a loss of pinna reflex at 20 KHz in mother guinea pigs treated during the late period of pregnancy. Histopathologically, no damages were detected in the cochlea of mother guinea pigs treated with NTL during the early or late period of pregnancy, whereas slight scattered loss of hair cells was seen in the vestibulum. However, GM at dose of 45 mg/kg, caused an incomplete scattered loss of outer hair cells in the spiral organ, moderate atrophy of the spiral ganglion cells and a partial loss of hair cells in the vestibular organs in mother guinea pigs treated during the late period of pregnancy. In newborn guinea pig from the pregnant one treated with NTL during the early period of pregnancy, there was no loss of pinna reflex. The same results were obtained in newborn guinea pigs from the pregnant ones treated with either NTL or GM during the late period of pregnancy. No histopathological damages were detected. The present study suggests that NTL has a minimal effect on the auditory and vestibular organs in pregnant guinea pigs and the newborn and is considered to be 1 of the aminoglycosides with low ototoxic potential.
研究了奈替米星(NTL)对妊娠豚鼠(哈特利品系)及其新生仔的耳毒性,并与庆大霉素(GM)进行了比较。在妊娠第0天至第35天(妊娠早期)或妊娠第42天至分娩前1天(妊娠晚期),给妊娠豚鼠肌肉注射剂量为90mg/kg的NTL。在妊娠晚期,给妊娠豚鼠肌肉注射剂量为45mg/kg的GM或生理盐水。妊娠早期接受NTL的5只母鼠中有4只死亡,妊娠晚期接受TNL的7只母鼠中有4只死亡,妊娠晚期接受GM的4只母鼠中有2只死亡。在妊娠早期或晚期接受NTL治疗的母豚鼠中,未检测到2至20kHz频率范围内的耳廓反射丧失。GM导致妊娠晚期接受治疗的母豚鼠在20kHz时耳廓反射丧失。组织病理学检查显示,妊娠早期或晚期接受NTL治疗的母豚鼠耳蜗未发现损伤,而在前庭可见轻微散在的毛细胞丢失。然而,剂量为45mg/kg的GM导致妊娠晚期接受治疗的母豚鼠螺旋器中外毛细胞不完全散在丢失、螺旋神经节细胞中度萎缩以及前庭器官中部分毛细胞丢失。妊娠早期接受NTL治疗的妊娠豚鼠所生的新生豚鼠未出现耳廓反射丧失。妊娠晚期接受NTL或GM治疗的妊娠豚鼠所生的新生豚鼠也得到了相同的结果。未检测到组织病理学损伤。本研究表明,NTL对妊娠豚鼠及其新生仔的听觉和前庭器官影响极小,被认为是耳毒性潜力较低的氨基糖苷类药物之一。