Effects of combined zidovudine/lopinavir/ritonavir therapy during rat pregnancy: morphological aspects

Effects of combined zidovudine/lopinavir/ritonavir therapy during rat pregnancy: morphological aspects

Author Carvalho, Luisa Patricia Fogarolli de Autor UNIFESP Google Scholar
Simoes, Ricardo Santos Autor UNIFESP Google Scholar
Wagner, A. Google Scholar
Tavella, J. S. Google Scholar
Oliveira-Filho, Ricardo Martins Autor UNIFESP Google Scholar
Kulay Júnior, Luiz Autor UNIFESP Google Scholar
Nakamura, Mary Uchiyama Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Jose do Rosario Velano
Universidade de São Paulo (USP)
Abstract Purpose: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.
Keywords Zidovudine
Lopinavir
Ritonavir
Toxicology
Pregnancy
Rats
Language English
Date 2013-01-01
Published in Clinical And Experimental Obstetrics & Gynecology. Montreal: I R O G Canada, Inc, v. 40, n. 3, p. 345-349, 2013.
ISSN 0390-6663 (Sherpa/Romeo, impact factor)
Publisher I R O G Canada, Inc
Extent 345-349
Origin http://www.irog.net/download/?magazine=113
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000343848400009
URI http://repositorio.unifesp.br/11600/43298

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