de Carvalho L P Fogarolli, Simões R S, Wagner A, Tavella J S, Oliveira-Filho R M, Kulay L, Nakamura M Uchiyama
Department of Obstetrics, São Paulo Federal University UNIFESP), São Paulo, Brazil.
Clin Exp Obstet Gynecol. 2013;40(3):345-9.
To evaluate the morphological aspects in rats subjected to an association of the antiretroviral drugs zidovudine/lopinavir/ritonavir in different doses administered throughout the gestational period.
Forty pregnant rats were randomly allocated into four groups: control (Ctrl) and experimental (Exp1, Exp2, and Exp3), which received zidovudine/lopinavir/ritonavir in the doses of 10/13.3/3.3, 30/39.9/9.9, and 90/119.7/29.7 mg/kg per day from the first to the 20th day of pregnancy, respectively. At term, the animals were euthanized and maternal and fetal organ samples were removed for morphological analysis.
No major changes were identified in the group treated with the lowest dosing compared with the control. In group Exp2, the authors found hepatocytes with eosinophilic cytoplasm, pyknotic nuclei, and vasodilation. The proximal convoluted tubules of maternal kidneys showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. In the group treated with the highest dose (Exp3); the morphological changes in the maternal kidneys and livers were similar and more pronounced than those found in Exp2. The maternal pancreas of groups Exp2 and Exp3 evidenced moderate and progressive signs of tissue damage. The morphological features of all fetal livers, kidneys, and pancreases were normal.
High doses of zidovudine/lopinavir/ritonavir association during the entire rat pregnancy period can cause definite morphological changes in maternal liver, kidneys, and pancreas. On the other hand, the corresponding fetal organs were not affected.
评估在整个妊娠期给予不同剂量抗逆转录病毒药物齐多夫定/洛匹那韦/利托那韦的大鼠的形态学方面。
40只怀孕大鼠被随机分为四组：对照组（Ctrl）和实验组（Exp1、Exp2和Exp3），分别在怀孕第1天至第20天接受剂量为10/13.3/3.3、30/39.9/9.9和90/119.7/29.7mg/kg的齐多夫定/洛匹那韦/利托那韦。足月时，对动物实施安乐死，并取出母体和胎儿的器官样本进行形态学分析。
与对照组相比，最低剂量治疗组未发现重大变化。在Exp2组中，作者发现肝细胞胞质嗜酸性、核固缩以及血管扩张。母体肾脏的近端曲管显示嗜酸性区域和核深染，以及血管扩张迹象。在最高剂量治疗组（Exp3）中，母体肾脏和肝脏的形态学变化相似，且比Exp2组更明显。Exp2组和Exp3组的母体胰腺有中度且进行性的组织损伤迹象。所有胎儿肝脏、肾脏和胰腺的形态特征均正常。
在大鼠整个孕期给予高剂量的齐多夫定/洛匹那韦/利托那韦联合用药可导致母体肝脏、肾脏和胰腺出现明确的形态学变化。另一方面，相应的胎儿器官未受影响。
