Akiyoshi M, Nakada H, Akashi O, Waki Y, Hara T, Harada S, Deguchi T
Jpn J Antibiot. 1985 Feb;38(2):203-11.
Ototoxic effect of micronomicin (MCR) in intravenous drip administration was investigated in guinea pigs (300--400 g) receiving MCR for 30 days at dose of 50 and 100 mg/kg, respectively. MCR was dissolved in physiologic saline and 1.5 ml of the solution was infused through polyethylene tube into the left external jugular vein with Perista mini-pump for 60 minutes every day after measurement of body weight. Auditory impairment was monitored by pinna reflex audiometry. Pinna reflex loss was not detected in any animal in frequency range (0.5 to 20 kHz). Cochlear hair cell damage generally was of mild degree. Two out of 6 animals treated with MCR 50 mg/kg (Table 1) showed outer hair cell loss confined to unilateral basal end and posterior 3/4 of the first turn, respectively. Outer hair cell loss was noticed in 4 of 9 animals receiving MCR 100 mg/kg (Table 2); much less extensive in 3 animals, unsymmetrical slightly extensive in remaining 1. Unilateral circumscribed loss of inner hair cells was noticed at lower part of the hook in the latter one. Vestibular hair cell loss was scattered and less extensive and occurred in 4 of the 6 50 mg/kg given animals and in 7 of the 9 100 mg/kg ones. Comparison in incidence and extension of the outer hair cell loss of the cochlea (Tables 3, 4) in the present study and previous ones on the ototoxic effect of MCR in intramuscular and intravenous administration suggests that there was no distinct difference in enhancement of the ototoxic effect in the intravenous drip administration.
在体重300 - 400克的豚鼠中,研究了小诺米星(MCR)静脉滴注给药的耳毒性作用。豚鼠分别接受剂量为50毫克/千克和100毫克/千克的MCR,持续30天。MCR溶解于生理盐水中,每天在测量体重后,用Perista微型泵通过聚乙烯管将1.5毫升该溶液注入左颈外静脉,持续60分钟。通过耳廓反射听力测定法监测听觉损伤情况。在频率范围(0.5至20千赫)内,未在任何动物中检测到耳廓反射丧失。耳蜗毛细胞损伤一般程度较轻。接受50毫克/千克MCR治疗的6只动物中有2只(表1)分别出现外毛细胞丧失,局限于单侧基底端和第一圈的后3/4。接受100毫克/千克MCR的9只动物中有4只出现外毛细胞丧失(表2);3只动物的外毛细胞丧失范围小得多,其余1只不对称且范围稍大。在后者中,在内耳钩的下部发现了单侧局限性内毛细胞丧失。前庭毛细胞丧失分散且范围较小,在接受50毫克/千克给药的6只动物中有四只出现,在接受100毫克/千克给药的9只动物中有7只出现。本研究中关于耳蜗外毛细胞丧失的发生率和范围(表3、4)与之前关于MCR肌肉注射和静脉注射耳毒性作用的研究进行比较表明,静脉滴注给药时耳毒性作用的增强没有明显差异。