Mallié J P, Coulon G, Billerey C, Faucourt A, Morin J P
Laboratoire de Néphrologie, Université de Nancy I, France.
Kidney Int. 1988 Jan;33(1):36-44. doi: 10.1038/ki.1988.6.
Pregnant Wistar females were treated with gentamicin (G), netilmicin (N) or amikacin (A) during two periods of pregnancy covering organogenesis and the beginning of nephrogenesis. Deliveries occurred normally. We studied functional effects--influence of sex, litter size, diuresis, creatinine clearance, G-kidney concentration, and kidney morphological alterations--in rat neonates on day 1 of life. After G and N, the creatinine clearance of the neonates was decreased according to the dosage given to the mother. Whatever the aminoglycoside, kidneys presented proximal tubular alterations (close to those observed in adults) at protonic microscopy and, with electron microscopy, some modifications of distal tubules and of mature and immature glomeruli. It is concluded that the developing kidney can be altered after treating pregnant mothers with aminoglycosides. This model of in utero-induced nephrotoxicity is dose-dependent. Mature and/or immature structures could be affected. The toxicity of the investigated antibiotics could be asserted as G greater than or equal to N greater than A.
在怀孕的两个阶段,即器官形成期和肾发生开始期,对怀孕的Wistar雌性大鼠使用庆大霉素(G)、奈替米星(N)或阿米卡星(A)进行治疗。分娩正常进行。我们研究了出生第一天大鼠新生儿的功能影响——性别、窝仔数、利尿、肌酐清除率、肾脏G浓度的影响以及肾脏形态学改变。使用G和N后,新生儿的肌酐清除率根据给予母亲的剂量而降低。无论使用哪种氨基糖苷类药物,在光学显微镜下,肾脏均呈现近端肾小管改变(类似于在成人中观察到的改变),在电子显微镜下,远端肾小管以及成熟和未成熟肾小球有一些改变。得出的结论是,用氨基糖苷类药物治疗怀孕母亲后,发育中的肾脏可能会受到影响。这种宫内诱导肾毒性的模型是剂量依赖性的。成熟和/或未成熟结构可能会受到影响。所研究抗生素的毒性可以确定为G≥N>A。