A morphological and biochemical appraisal of the liver and renal effects of lamivudine on rat pregnancy.
No data exist on the perinatal safety of lamivudine alone, as it is used in combination with other antiretroviral agents. Until now, only preliminary data on the lamivudine-zidovudine combination have been available, thus we decided to examine the gross maternal and fetal effects of lamivudine administered alone during the entire period of rat pregnancy. Forty pregnant animals were assigned at random to four groups (C1 = control; E1 = 5 mg/kg; E2 = 15 mg/kg; E3 = 45 mg/kg) from day 0 up to the 20th day of gestation. These doses were divided into two daily administrations by gavage. Controls (n = 10) received distilled water in the same schedule. At term-pregnancy, the rats were deeply anesthetized and blood samples were collected for alanine and aspartate aminotransferases, creatinine and urea determinations. Fragments of maternal and fetal livers and kidneys were taken and processed for histopathological study. In all groups blood transaminases were within the normal limits, as were the levels of creatinine and urea, thus indicating that treatment with lamivudine during the entire gestation was essentially devoid of liver or kidney effects which could result in altered metabolic parameters. Morphological (light microscopy) studies revealed that no significant effects of the drug could be detected regarding either maternal or fetal organs of the E1 and E2 groups. However, the maternal hepatocytes in the E3 group showed heterochromatic nuclei. In addition, there was some fatty infiltration, congested sinusoids and portal dilatation. Maternal kidneys in the E3 group revealed vascular dilation around the convoluted tubules. It is concluded that only doses of lamivudine used during the entire gestation in doses well above the usual human doses could be considered to be potentially hepatotoxic for the pregnant rat.
Pontes
R D V
RD
Federal University of São Paulo, School of Medicine, Brazil.
Amed
A M
AM
Simões
R S
RS
Oliveira-Filho
R M
RM
Simões
M J
MJ
Kulay
L Júnior
LJ
D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects*; D005260:Female; D007668:Kidney / Q000187:drug effects*; D019259:Lamivudine / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D019380:Anti-HIV Agents; D019259:Lamivudine