Desenvolvimento embrionário em ratas tratadas com tacrolimus durante a fase de pré-implantação

Abstract

PURPOSE: to evaluate the toxicity of tacrolimus on embryonic development in rats treated during the tubal transit period. METHODS: sixty Wistar rats were distributed into four groups (15 animals each), which received different doses of tacrolimus through intragastric administration: (T1) 1.0 mg/kg/day, (T2) 2.0 mg/kg/day and (T3) 4.0 mg/kg/day. The control group (C) received distilled water. The rats were observed daily to detect clinical signs of toxicity. The treatments were performed from the first to the fifth day of pregnancy. The following maternal variables were analyzed: body, ovary, liver, and kidney weights, food intake, number of corpora lutea, implants, alive and dead fetuses, and implantation rates. The fetuses and placentae were weighed and the former were observed in order to detect external malformation. Statistical analysis was performed by one way: analysis of variance (ANOVA), folowed by the Dunnet test (alpha=0.05). RESULTS: there were no signs of maternal toxicity, such as body weight loss, decrease in food intake or in organ weights (p>0.05). There was also no significant difference among weights of fetuses (C: 1.8±0.6; T1: 2.2±0.5; T2: 1.9±0.5 and T3: 2.0±0.5 g) and placentae (C: 1,6±0.4; T1: 1.5±0.4; T2: 1.8±0.4 e T3: 1.6±0.4 g), with p>0.05; no external malformation was detected in the fetuses. CONCLUSIONS: the administration of tacrolimus to pregnant rats during the tubal transit period does not seem to generate any toxic effect to mother or embryo.