Hepatotoxicity of N, N-dimethylformamide (DMF) in acute poisoning with the veterinary euthanasia drug T-61.
1. We report on a patient who was resuscitated after a suicide attempt with the veterinary euthanasia product T-61 and treated with N-acetylcysteine (NAC) to prevent hepatotoxicity from N,N-dimethylformamide (DMF), the solvent of T-61. 2. Serum concentrations of DMF were high as compared with values published on occupational exposure. 3. The patient showed only a transient increase in liver enzymes with eventually a full recovery. 4. The hepatoprotective effect of NAC was studied in a rat model using the rise in serum sorbitol dehydrogenase (SDH) as a marker for DMF-induced hepatotoxicity. 5. Four series of randomized, controlled and double-blind experiments were carried out and consistently showed a lower increase in SDH in NAC-treated animals in each series. The difference was statistically significant only when the data of the 4 series were pooled. This is probably due to the large interindividual variations in the effect of DMF. 6. We hypothesize that in the rat NAC may have a protective effect. Whether NAC is also protective in patients, in which it is administered after exposure to DMF, cannot be concluded from the present experiments.
Buylaert
W
W
Department of Emergency Medicine, University Hospital Gent, Belgium.
Calle
P
P
De Paepe
P
P
Verstraete
A
A
Samyn
N
N
Vogelaers
D
D
Vandenbulcke
M
M
Belpaire
F
F
D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000577:Amides / Q000506:poisoning* / Q000633:toxicity; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004126:Dimethylformamide / Q000493:pharmacokinetics / Q000506:poisoning* / Q000633:toxicity; D004338:Drug Combinations; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D008107:Liver Diseases / Q000097:blood / Q000517:prevention & control*; D008297:Male; D000644:Quaternary Ammonium Compounds / Q000506:poisoning* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013406:Suicide, Attempted; D013748:Tetracaine / Q000506:poisoning* / Q000633:toxicity
D000577:Amides; D004338:Drug Combinations; D016166:Free Radical Scavengers; D000644:Quaternary Ammonium Compounds; D013748:Tetracaine; C015591:T 61; D004126:Dimethylformamide; D007064:L-Iditol 2-Dehydrogenase; D000111:Acetylcysteine