title: Administration of benznidazole, a chemotherapeutic agent against Chagas disease, to pregnant rats. Covalent binding of reactive metabolites to fetal and maternal proteins.
abstract: Benznidazole (Bz) (N-benzyl-2-nitro-1-imidazole acetamide) is one of the drugs used in the chemotherapy of Chagas' disease though there is scarce data at present about its toxicological properties. The aim of this study was to obtain some very preliminary information about the potential risks for the fetuses when Bz is administered to pregnant women. With that purpose, 14C-Bz was orally administered to rats at twenty days of pregnancy. The animals were sacrificed 1, 3 or 6 hr after administration and the different tissues and fetuses analyzed for 14C from 14C-Bz bound covalently to proteins. It was observed that the drug is readily absorbed, crosses the placental barrier and reaches the fetuses. It is also activated in vivo to reactive metabolites that bind covalently to maternal and fetal proteins. In the light of the present results it would be wise to carefully consider the need and unknown risk of Bz therapy in pregnant women, until further appropriate studies on the developmental toxicology of Bz become available.
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy; D005260:Female; D005333:Fetus / Q000378:metabolism*; D009153:Mutagens; D009593:Nitroimidazoles / Q000378:metabolism / Q000633:toxicity*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D009153:Mutagens; D009593:Nitroimidazoles; C009999:benzonidazole