Evaluation of the protective activity of deferiprone, an aluminum chelator, on aluminum-induced developmental toxicity in mice

Background: Since deferiprone can be an effective chelating agent for the t reatment of aluminum (AI) overload, in the present study we investigated wh ether this chelator could protect against AI-induced maternal and developme ntal toxicity in mice. Methods: A single oral dose of Al nitrate nonahydrate (1,327 mg/kg) was giv en on gestation day 12, the most sensitive time for AI-induced maternal and developmental toxic effects in mice. At 2, 24, 48, and 72 hr thereafter, d eferiprone was given by gavage at 0 and 24 mg/kg. Cesarean sections were pe rformed on day 18 of gestation and fetuses were examined for malformations and variations. Results: Aluminum-induced maternal toxicity was evidenced by significant re ductions in body weight gain, corrected body weight change, and food consum ption. Developmental toxicity was evidenced by a significant decrease in fe tal weight per litter and an increase in the total number of fetuses and li tters showing bone retardation. No beneficial effects of deferiprone on the se adverse effects could be observed. By contrast, a more pronounced decrea se in maternal weight gain and corrected body weight change, as well as a h igher number of litters with fetuses showing skeletal variations was noted in the group exposed to Al nitrate and treated with deferiprone at 24 mg/kg . Conclusions: According to the current results, deferiprone would not be eff ective to prevent At-induced maternal and embryo/fetal toxicity in mice. Te ratology 62:86-92, 2000. (C) 2000 Wiley-Liss, Inc.