Some observations on dimethylformamide hepatotoxicity.
Dimethylformamide (DMF) and its biotransformation products monomethylformamide (MMF) and formamide (F) were administered intraperitoneally to rats. Serum levels of sorbitol dehydrogenase (SDH) were studied at 3 h intervals from 9 h to 30 h after administration. Liver histology at 12, 21 and 30 h proved elevated SDH levels to be an indication of liver necrosis. DMF 479 mg/kg produced elevated enzyme levels at 27 h and 30 h while half the dose, 240 mg/kg, produced elevated levels from 15 h onwards. MMF 387 mg/kg produced elevated SDH levels at all times studied. F did not give elevated levels at any time. DMF (479 mg/kg) and MMF (387 mg/kg) administered simultaneously produced elevated SDH levels from 24 h onwards. These findings suggest that DMF hepatotoxicity is mediated by a degradation product of MMF and that DMF delays the hepatotoxic effect induced by MMF.
D000818:Animals; D004126:Dimethylformamide / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007064:L-Iditol 2-Dehydrogenase / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D004126:Dimethylformamide; D007064:L-Iditol 2-Dehydrogenase