Fontes T M Pereira, Nakamura M U, Mattar R, Simões R S, Wagner A, de Carvalho A Moreira, Espiridião S, Kulay L
Department of Obstetrics and Gynecology, Federal University of São Paulo School of Medicine (UNIFESP-EPM), São Paulo, SP, Brazil.
Clin Exp Obstet Gynecol. 2011;38(2):126-30.
To evaluate biochemical and morphological effects on rats submitted to three different doses of the association zidovudine and ritonavir administered throughout pregnancy.
Forty pregnant EPM-1 Wistar rats weighing about 200 g were randomly divided into the control group (Ctr = drug vehicle control, n = 10) and three experimental ones which were treated with an oral solution of zidovudine/ritonavir (Exp1 = 10/20 mg/kg bw, n = 10; Exp2 = 30/60 mg/kg bw, n = 10; Exp3 = 90/180 mg/kg bw, n = 10) from 'day 0' up to the 20th day of pregnancy. At term (20th day) the rats were anesthetized. Blood and fetal and maternal organ samples (livers and kidneys) were taken for morphological and biochemical analyses.
Upon histological examinations fetal livers and kidneys appeared normal. In contrast the maternal samples revealed structural alterations. Maternal kidneys of the three experimental groups exhibited progressive and dose-dependent histological alterations; liver alterations were detected only in Exp3. Blood levels of AST and ALT were not significantly different from the control group but urea and creatinine levels were lower in groups Exp3 and Exp1.
The administration of zidovudine plus ritonavir throughout rat pregnancy can cause morphological as well as functional changes in maternal kidneys.
评估在整个孕期给予大鼠三种不同剂量齐多夫定与利托那韦联合用药后的生化和形态学影响。
将40只体重约200 g的妊娠EPM - 1系Wistar大鼠随机分为对照组（Ctr = 药物赋形剂对照组，n = 10）和三个实验组，从妊娠“第0天”至第20天，分别用齐多夫定/利托那韦口服溶液进行治疗（Exp1 = 10/20 mg/kg体重，n = 10；Exp2 = 30/60 mg/kg体重，n = 10；Exp3 = 90/180 mg/kg体重，n = 10）。足月时（第20天），将大鼠麻醉。采集血液以及胎儿和母体器官样本（肝脏和肾脏）进行形态学和生化分析。
组织学检查显示胎儿肝脏和肾脏外观正常。相比之下，母体样本显示出结构改变。三个实验组的母体肾脏呈现出进行性且剂量依赖性的组织学改变；仅在Exp3组检测到肝脏改变。AST和ALT的血液水平与对照组无显著差异，但Exp3组和Exp1组的尿素和肌酐水平较低。
在大鼠整个孕期给予齐多夫定加利托那韦可导致母体肾脏出现形态以及功能变化。
