Liver injury and alterations of hepatic microsomal monooxygenase system due to dimethylformamide (DMF) in rats.
The effects of repeated exposure to N, N-dimethylformamide (DMF) on the liver and the hepatic microsomal monooxygenase system were investigated. DMF was administered to Wistar male rats by subcutaneous (s.c.) injection at 0.5 ml/kg body weight daily for 1-17 days. Macroscopically, mild liver swelling was observed and liver weights significantly increased after 3 days of exposure to DMF respectively. Hematological changes were not observed. In exposed rats, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase significantly increased after 3 and 7 days of exposure to DMF. After 17 days of exposure to DMF, transaminases decreased compared to the 7 days. Hepatic microsomal cytochrome P-450 tended to decrease after 3 days of exposure DMF and decreased by 34% after 7 days and 25% after 17 days. Aminopyrine N-demethylase activity depressed significantly while aniline hydroxylase activity showed no change after 3 days of exposure to DMF. These results indicate that DMF alters the hepatic microsomal monooxygenase system. These findings may greatly contribute to the elucidation of the pathogenesis of DMF hepatotoxicity.
NTT Kitakyushu Hospital, Kitakyushu.
K
K
Imazu
K
K
Fujishiro
N
N
Inoue
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004126:Dimethylformamide / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D004126:Dimethylformamide; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase