Embryotoxicity of meglumine antimoniate in the rat.
Meglumine antimoniate (MA) is a pentavalent antimonial (Sb(V)) drug used to treat leishmaniasis. Despite the fact that Sb(V) organic compounds have been used in clinical practice for more than 50 years, information on their safety during pregnancy is still scanty. This study was undertaken to evaluate the embryo/fetotoxicity of MA in the rat. Wistar rats were treated subcutaneously (s.c.) with MA (300 mg Sb(V)/kg body wt/day) on days 6 through 15 of pregnancy or with a higher dose (3 x 300 mg Sb(V)/kg body wt) on day 11 only. A control group treated with saline on days 6 through 15 and an untreated control group were evaluated as well. Cesarean sections were performed on day 21. No maternal toxicity and no reduction of fetal weight were noted in the groups treated with MA. The repeated administration of MA (days 6 through 15), but not the acute treatment (day 11), enhanced embryolethality. Treatment with MA on days 6 through 15 also caused a higher incidence of an atlas bone anomaly that occurs spontaneously at very low frequencies in our rat strain. These findings indicated that repeated administration of MA was embryolethal and teratogenic in rats.
Paumgartten
F J
FJ
Laboratory of Environmental Toxicology, National School of Public Health, Oswaldo Cruz Foundation, Av. Brasil 4365, RJ 21045-900, Rio de Janeiro, Brazil. paum@manguinhos.ensp.fiocruz.br
Chahoud
I
I
D000014:Abnormalities, Drug-Induced; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000633:toxicity*; D001270:Cervical Atlas / Q000002:abnormalities / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D020567:Fetal Weight / Q000187:drug effects; D007279:Injections, Subcutaneous; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000633:toxicity*; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests
D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D013723:Teratogens; D008536:Meglumine; D000077485:Meglumine Antimoniate