In vivo and in vitro oxidative biotransformation of dimethylformamide in rat.
In rats and in humans, dimethylformamide (DMF) is mainly metabolized into N-hydroxymethyl-N-methylformamide (DMF-OH). The in vitro oxidation of DMF by rat liver microsomes is decreased in the presence of catalase and superoxide dismutase. The radical scavengers, dimethylsulfoxide (DMSO), tertiary butyl alcohol (t-butanol), aminopyrine, hydroquinone and trichloroacetonitrile reduce the oxidation of DMF to DMF-OH in vitro and in vivo. Conversely, DMF inhibits the demethylation of DMSO, t-butanol and aminopyrine. The addition of iron-EDTA to the incubation system induces the production of N-methylformamide (NMF) from DMF. These results support the hypothesis that the metabolic pathway leading from DMF to DMF-OH and NMF involves hydroxyl radicals. Superoxide radical and hydrogen peroxide take part in the metabolic process. DMF is preferentially metabolized into DMF-OH. NMF appears mainly when the production of hydroxyl radicals is stimulated, the methyl group being recovered as formic acid.
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001711:Biotransformation / Q000187:drug effects; D004126:Dimethylformamide / Q000031:analogs & derivatives / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D005559:Formamides / Q000378:metabolism; D005561:Formates / Q000378:metabolism; D005609:Free Radicals; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014969:Xanthine Oxidase / Q000378:metabolism
D005290:Ferric Compounds; D005559:Formamides; D005561:Formates; D005609:Free Radicals; D006878:Hydroxides; D007042:Hypoxanthines; C030544:formic acid; C042331:N-hydroxymethyl-N-methylformamide; D019271:Hypoxanthine; D017665:Hydroxyl Radical; D004126:Dimethylformamide; D004492:Edetic Acid; D014969:Xanthine Oxidase; C019179:Fe(III)-EDTA; D001205:Ascorbic Acid; C002950:methylformamide