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暴露于拉替拉韦胎盘转运的新生大鼠中的微核红细胞。

Micronucleated erythrocytes in newborn rats exposed to raltegravir placental transfer.

作者信息

Torres-Mendoza Blanca Miriam, Coronado-Medina Damharis Elizabeth, Gómez-Meda Belinda Claudia, Vázquez-Valls Eduardo, Zamora-Perez Ana Lourdes, Lemus-Varela María de Lourdes, Zúñiga-González Guillermo Moisés

机构信息

División de Neurociencias, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, 44340 Guadalajara, JAL, Mexico ; Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44350 Guadalajara, JAL, Mexico.

División de Neurociencias, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, 44340 Guadalajara, JAL, Mexico ; Maestría en Nutrición Clínica, Universidad del Valle de Atemajac, 45050 Zapopan, JAL, Mexico.

出版信息

Biomed Res Int. 2014;2014:851820. doi: 10.1155/2014/851820. Epub 2014 May 25.

Abstract

The use of raltegravir in treating HIV/AIDS has been proposed due to its effectiveness in suppressing high loads of HIV RNA in pregnant women, thus preventing infection of the fetus. However, administration of raltegravir during pregnancy produces a compound which is transferred to high concentrations to the offspring. The objective of this study is to evaluate the transplacental genotoxic effect of raltegravir in newborn rats. We evaluated the number of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) in the peripheral blood samples of the offspring of Wistar rats treated 6 days before birth with oral administration of raltegravir. The animals were randomly assigned to five groups as follows: raltegravir at doses of 15, 30, or 60 mg/day, cyclophosphamide 10 mg/kg (positive control), or 0.5 ml of sterile water (negative control). In addition, the effect of these drugs on the weight and height of newborns was assessed. There were no differences in the number of MNE, MNPCE, and PCE, and a slight decrease in the weight and height was observed in the offspring of the rat mothers treated with raltegravir. Genotoxicity studies are required in pregnant women to determine the risk of using raltegravir to the fetuses.

摘要

由于雷特格韦在抑制孕妇体内高负荷的HIV RNA方面有效,从而可预防胎儿感染,因此有人提出使用雷特格韦治疗HIV/AIDS。然而,孕期使用雷特格韦会产生一种化合物,该化合物会以高浓度转移至后代体内。本研究的目的是评估雷特格韦对新生大鼠的经胎盘遗传毒性作用。我们评估了在出生前6天经口给予雷特格韦治疗的Wistar大鼠后代外周血样本中的微核红细胞(MNE)、微核多染红细胞(MNPCE)和多染红细胞(PCE)数量。将动物随机分为五组,如下:剂量为15、30或60 mg/天的雷特格韦组、10 mg/kg环磷酰胺组(阳性对照)或0.5 ml无菌水组(阴性对照)。此外,评估了这些药物对新生儿体重和身高的影响。MNE、MNPCE和PCE的数量没有差异,在用雷特格韦治疗的大鼠母亲的后代中观察到体重和身高略有下降。需要对孕妇进行遗传毒性研究,以确定使用雷特格韦对胎儿的风险。

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本文引用的文献

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Pharmacokinetic and safety of raltegravir in pregnancy.拉替拉韦在妊娠期的药代动力学及安全性
Eur J Clin Pharmacol. 2012 Aug;68(8):1231-2. doi: 10.1007/s00228-012-1250-5. Epub 2012 Mar 1.
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Role of raltegravir in the management of HIV-1 infection.雷特格韦在HIV-1感染管理中的作用。
HIV AIDS (Auckl). 2011;3:81-92. doi: 10.2147/HIV.S13985. Epub 2011 Jul 15.

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