Development toxicity effects of atorvastatin and rosuvastatin in mice

Abstract

Background: Statins reduce the risk, morbidity and mortality associated with cardiovascular events, and generally considered safe to use but their safety in pregnancy is not known. Statins are considered potentially teratogenic and are contraindicated in pregnancy on the basis of lack of evidence. Objectives: The objectives of the study were to determine and compare the developmental toxicity effects including teratogenic and offspring weight effect of rosuvastatin and atorvastatin in time mated mice. Methods: Fifty six Balb c mice were divided into seven experimental groups of eight mice each. Atorvastatin and rosuvastatin were administered at doses of 10, 40, 100mg/kg/day via oral gavage route once every day for 7 days prior to the mating and continued during the mating and pregnancy period up to delivery. Maternal weight changes and miscarriages were monitored during the pregnancy period. The mice were allowed a vaginal delivery and the offspring were weighed and assessed for gross morphological defects. Results: There was no dose related changes in litter size or suppressed maternal weight gain in the study groups. No significant differences when the control group was compared to the individual atorvastatin groups, rosuvastatin 10 and 100mg /kg (p > 0.05). The rosuvastatin 40 mg/kg had significantly lower birth weight compared with control (p =0.022) in post hoc analysis. No gross morphological defects were observed in all the offspring. Conclusions: No developmental toxicity including teratogenic effects were observed on atorvastatin and rosuvastatin at 10, 40 and 100mg/kg in a mice model.