In vivo and in vitro oxidative biotransformation of dimethylformamide in rat |
| |
Authors: | V. Scailteur R. Lauwerys |
| |
Affiliation: | Unité de Toxicologie Industrielle & Médecine du Travail, Faculté de Médecine, Université Catholique de Louvain, 30.54 Clos Chapelle-aux-Champs, B-1200 Brussels Belgium |
| |
Abstract: | 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. |
| |
Keywords: | Metabolism Rat Dimethylformamide N-Hydroxymethyl N-methylformamide N-Methylformamide Hydroxyl radicals |
本文献已被 ScienceDirect 等数据库收录! |
|