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宫内氨基糖苷类药物诱导的大鼠新生儿肾毒性。

In utero aminoglycosides-induced nephrotoxicity in rat neonates.

作者信息

Mallié J P, Coulon G, Billerey C, Faucourt A, Morin J P

机构信息

Laboratoire de Néphrologie, Université de Nancy I, France.

出版信息

Kidney Int. 1988 Jan;33(1):36-44. doi: 10.1038/ki.1988.6.

DOI:10.1038/ki.1988.6
PMID:3352159
Abstract

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.

摘要

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。

相似文献

1
In utero aminoglycosides-induced nephrotoxicity in rat neonates.宫内氨基糖苷类药物诱导的大鼠新生儿肾毒性。
Kidney Int. 1988 Jan;33(1):36-44. doi: 10.1038/ki.1988.6.
2
Comparative nephrotoxicity of hydroxygentamicin and other aminoglycosides in rats.庆大霉素与其他氨基糖苷类药物对大鼠的肾毒性比较
Fundam Appl Toxicol. 1984 Aug;4(4):558-67. doi: 10.1016/0272-0590(84)90045-9.
3
[Experimental study of nephrotoxicity: effects, on the newborn rat kidney, of aminoglycoside administration during gestation].[肾毒性的实验研究:孕期给予氨基糖苷类药物对新生大鼠肾脏的影响]
Nephrologie. 1989;10(1):27-31.
4
Gentamicin, netilmicin, dibekacin, and amikacin nephrotoxicity and its relationship to tubular reabsorption in rabbits.庆大霉素、奈替米星、地贝卡星和阿米卡星对家兔的肾毒性及其与肾小管重吸收的关系。
Antimicrob Agents Chemother. 1984 Feb;25(2):168-72. doi: 10.1128/AAC.25.2.168.
5
In-utero gentamicin-induced nephrotoxicity in rats.宫内庆大霉素诱导的大鼠肾毒性
Pediatr Pharmacol (New York). 1986;5(4):229-39.
6
Choice of drug and dosage regimen. Two important risk factors for aminoglycoside nephrotoxicity.药物及给药方案的选择。氨基糖苷类药物肾毒性的两个重要风险因素。
Am J Med. 1986 Jun 30;80(6B):115-8. doi: 10.1016/0002-9343(86)90488-2.
7
Nonparallel nephrotoxicity dose-response curves of aminoglycosides.氨基糖苷类药物的非平行肾毒性剂量反应曲线。
Antimicrob Agents Chemother. 1981 Jun;19(6):1024-8. doi: 10.1128/AAC.19.6.1024.
8
The nephrotoxic potential of netilmicin as determined in a rat model.在大鼠模型中测定的奈替米星的肾毒性潜力。
Scand J Infect Dis Suppl. 1980;Suppl 23:82-90.
9
Comparative nephrotoxicity of four aminoglycosides: biochemical and ultrastructural modifications of lysosomes.四种氨基糖苷类药物的比较肾毒性:溶酶体的生化及超微结构改变
Adv Nephrol Necker Hosp. 1983;12:253-75.
10
Apoptosis in renal proximal tubules of rats treated with low doses of aminoglycosides.低剂量氨基糖苷类药物处理的大鼠肾近端小管中的细胞凋亡
Antimicrob Agents Chemother. 2000 Mar;44(3):665-75. doi: 10.1128/AAC.44.3.665-675.2000.

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Drug Saf. 2006;29(5):397-419. doi: 10.2165/00002018-200629050-00004.
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Gentamicin administered during gestation alters glomerular basement membrane development.孕期使用庆大霉素会改变肾小球基底膜的发育。
Antimicrob Agents Chemother. 1993 Jul;37(7):1510-7. doi: 10.1128/AAC.37.7.1510.
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Pediatr Nephrol. 1994 Aug;8(4):447-50. doi: 10.1007/BF00856528.
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Pediatr Nephrol. 1990 Jul;4(4):445-50. doi: 10.1007/BF00862534.