Alterations of hepatic drug metabolising system due to dimethylformamide (DMF).
The effect of repeated exposures to N, N-dimethylformamide (DMF) on the liver and the hepatic microsomal monooxygenase system and glutathione metabolizing enzymes were investigated. DMF was administered to Wistar male rats by subcutaneous (s.c.) injection at 1.0 ml/kg body weight (950 mg/kg), 3 times a week for 2 weeks. The gain in the body weight in the DMF group were suppressed compared with the control group at 2 week. The relative weight of the liver, spleen and kidney also appeared to increase in the DMF group as same as in the control group. Hematological examinations showed no changes. Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) did not change in the DMF group. Hepatic microsomal protein and cytochrome P-450 did significantly decrease by 30% and 38%, respectively, while there was no change in cytochrome b5, NADPH-cytochrome c reductase and NADH-ferricyanide reductase. Glutathione peroxidase (GPx) activity was not affected by DMF administration, while glutathione reductase (GR) and glutathione S-transferase, (GST) activity were significantly increased by 16% and 64%, respectively. These results indicate that DMF alters tke hepatic drug metabolizing system without significant increase of the serum transaminase levels. These findings may contribute to elucidate the mechanism of DMF hepatotoxicity.
Fujishiro
K
K
Occupational Health Training Center, University of Occupational and Environmental Health, Kitakyushu.
Imazu
K
K
Makita
Y
Y
Inoue
N
N
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004126:Dimethylformamide / Q000633:toxicity*; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008658:Inactivation, Metabolic; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000633:toxicity*
D012997:Solvents; D004126:Dimethylformamide; D003577:Cytochrome P-450 Enzyme System; D005980:Glutathione Reductase; D005982:Glutathione Transferase