title: Effects of combined zidovudine/lopinavir/ritonavir therapy during rat pregnancy: morphological aspects.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics, São Paulo Federal University UNIFESP), São Paulo, Brazil. luisa.fogarolli@gmail.com
authors.forename: L P Fogarolli
authors.initials: LP
authors.lastname: de Carvalho
authors.forename: R S
authors.initials: RS
authors.lastname: Simões
authors.forename: A
authors.initials: A
authors.lastname: Wagner
authors.forename: J S
authors.initials: JS
authors.lastname: Tavella
authors.forename: R M
authors.initials: RM
authors.lastname: Oliveira-Filho
authors.forename: L
authors.initials: L
authors.lastname: Kulay
authors.forename: M Uchiyama
authors.initials: MU
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D061466:Lopinavir / Q000008:administration & dosage*; D010179:Pancreas / Q000187:drug effects*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D019438:Ritonavir / Q000008:administration & dosage*; D015215:Zidovudine / Q000008:administration & dosage*
chemical_list: D017320:HIV Protease Inhibitors; D061466:Lopinavir; D015215:Zidovudine; D003404:Creatinine; D019438:Ritonavir