title: Effects of the association zidovudine plus ritonavir on the liver and kidneys of pregnant rats. Morphological and biochemical aspects.
abstract: OBJECTIVE
  To evaluate biochemical and morphological effects on rats submitted to three different doses of the association zidovudine and ritonavir administered throughout pregnancy.
  
  
  METHODS
  Forty pregnant EPM-1 Wistar rats weighing about 200 g were randomly divided into the control group (Ctr = drug vehicle control, n = 10) and three experimental ones which were treated with an oral solution of zidovudine/ritonavir (Exp1 = 10/20 mg/kg bw, n = 10; Exp2 = 30/60 mg/kg bw, n = 10; Exp3 = 90/180 mg/kg bw, n = 10) from 'day 0' up to the 20th day of pregnancy. At term (20th day) the rats were anesthetized. Blood and fetal and maternal organ samples (livers and kidneys) were taken for morphological and biochemical analyses.
  
  
  RESULTS
  Upon histological examinations fetal livers and kidneys appeared normal. In contrast the maternal samples revealed structural alterations. Maternal kidneys of the three experimental groups exhibited progressive and dose-dependent histological alterations; liver alterations were detected only in Exp3. Blood levels of AST and ALT were not significantly different from the control group but urea and creatinine levels were lower in groups Exp3 and Exp1.
  
  
  CONCLUSIONS
  The administration of zidovudine plus ritonavir throughout rat pregnancy can cause morphological as well as functional changes in maternal kidneys.
authors.affiliation: Department of Obstetrics and Gynecology, Federal University of São Paulo School of Medicine (UNIFESP-EPM), São Paulo, SP, Brazil. terezafontes@globo.com
authors.forename: T M Pereira
authors.initials: TM
authors.lastname: Fontes
authors.forename: M U
authors.initials: MU
authors.lastname: Nakamura
authors.forename: R
authors.initials: R
authors.lastname: Mattar
authors.forename: R S
authors.initials: RS
authors.lastname: Simões
authors.forename: A
authors.initials: A
authors.lastname: Wagner
authors.forename: A Moreira
authors.initials: AM
authors.lastname: de Carvalho
authors.forename: S
authors.initials: S
authors.lastname: Espiridião
authors.forename: L
authors.initials: L
authors.lastname: Kulay
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D019438:Ritonavir / Q000494:pharmacology* / Q000627:therapeutic use; D015215:Zidovudine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; D015215:Zidovudine; D019438:Ritonavir