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 treatment of aluminum (Al) overload, in the present study we investigated whether this chelator could protect against Al-induced maternal and developmental toxicity in mice.


METHODS
A single oral dose of Al nitrate nonahydrate (1,327 mg/kg) was given on gestation day 12, the most sensitive time for Al-induced maternal and developmental toxic effects in mice. At 2, 24, 48, and 72 hr thereafter, deferiprone was given by gavage at 0 and 24 mg/kg. Cesarean sections were performed on day 18 of gestation and fetuses were examined for malformations and variations.


RESULTS
Aluminum-induced maternal toxicity was evidenced by significant reductions in body weight gain, corrected body weight change, and food consumption. Developmental toxicity was evidenced by a significant decrease in fetal weight per litter and an increase in the total number of fetuses and litters showing bone retardation. No beneficial effects of deferiprone on these adverse effects could be observed. By contrast, a more pronounced decrease in maternal weight gain and corrected body weight change, as well as a higher 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 effective to prevent Al-induced maternal and embryo/fetal toxicity in mice.
Laboratory of Toxicology and Environmental Health, School of Medicine, University Rovira i Virgili, Reus 43201, Spain.
M L
ML
Albina
M
M
Bellés
D J
DJ
Sanchez
J L
JL
Domingo
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control*; D000284:Administration, Oral; D000535:Aluminum / Q000009:adverse effects / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000002:abnormalities; D000077543:Deferiprone; D005260:Female; D005317:Fetal Growth Retardation / Q000517:prevention & control; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D000535:Aluminum