Micronucleated erythrocytes in newborn rats exposed to raltegravir placental transfer.

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

doi:10.1155/2014/851820

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.

Highlights

Raltegravir or Isentress is the first antiretroviral integrase inhibitor approved by the US Food and Drug Administration in 2009 [1] and the European Medicines Agency in 2007 [2]
Raltegravir is among the available treatments used in highly active antiretroviral therapy (HAART) in treatmentnaıve patients with HIV/AIDS as was recommended in current guidelines [5], due to raltegravir being considered as a preferred treatment among the regimens for antiretroviral therapy-naıve patients regardless of the baseline viral load or CD4 cell count, accompanied by a low potential for drug interactions, both in naıve and treated individuals [6]
There were no statistically significant differences in the mean frequencies of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) in rat pups from raltegravir-treated mothers compared with the negative control group

Summary

Introduction

Raltegravir or Isentress is the first antiretroviral integrase inhibitor approved by the US Food and Drug Administration in 2009 [1] and the European Medicines Agency in 2007 [2]. Raltegravir prevents the integrase enzyme from incorporating HIV DNA into the host cell, reducing viral replication [3, 4]. Raltegravir clearance mechanism is by glucuronidation [7] which reduces its toxicity and protects the fetus from toxic drugs, such as antiretroviral and chemotherapeutic agents [8]. This drug is an alternative for patients with virologic failure to multidrug-resistant HIV [3, 4], with the advantage of not requiring protease inhibitors to potentiate its effect [9]. Raltegravir is among the available treatments used in highly active antiretroviral therapy (HAART) in treatmentnaıve patients with HIV/AIDS as was recommended in current guidelines [5], due to raltegravir being considered as a preferred treatment among the regimens for antiretroviral therapy-naıve patients regardless of the baseline viral load or CD4 cell count, accompanied by a low potential for drug interactions, both in naıve and treated individuals [6].

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Conclusion