Korean J Prev Med.  1999 Feb;32(1):88-94.

Induction of Hepatic Microsomal Cytochrome P450 by N,N-dimethylformamide in Sprague-Dawley Rats

• Koh SB
• Cha BS
• Kim KJ
• Kang SK
• Joung HS

Abstract

OBJECTIVES
In order to gain a better understanding of the mechanism of DMF toxicity, recent studies have focused on hepatic drug metabolizing enzymes. In this study, we investigated the effects of DMF on the induction of P450 and the activities of other related enzymes in rat liver microsomes.
METHODS
DMF was administered to male Sprague Daweley rats by intraperitoneal injection at 0(control), 450(D1), 900(D2), 1,800(D3) mg DMF/kg body weight in olive oil once a day for three days. Hepatic P450 was measured by method of Omura and Sato. We evaluated selective assays for the three drug metabolizing cytochrome P450 isoenzymes 1A1, 2B1 and 2E1.
RESULTS
The content of microsomal protein, P450 and b5 were tended to be decreased in DMF treated group, but they were not statistically significant. The activity of NADPH-cytochrome P450 reductase was significantly increased dose dependently(p<0.01), but the activity of NADH-b5 reductase was decreased in the treated group(p<0.01). The activities of PROD and EROD were not significant between control and treated group. The activities of pNPH in the DMF treated groups were higher than that of the control group(p<0.01). When Western immunoblottings were carried out utilizing three monoclonal antibodies which were specific against P4501A1/1, P4502B1/2 and P4502E1, the strong density band corresponding to P4502E1 was observed with the microsomes obtained from the rats treated with DMF. But there were no significant increased in the P4501A1/2 and P4502B1/2 band densities in immunoblotting.
CONCLUSIONS
These result suggested that P4502E1 was inducible by DMF and P4502E1 isozyme might be responsible for the hydroxylation of DMF to HMMF.

Keyword

N; N-dimetylformamide; cytochrome P450; P4502E1

MeSH Terms

Animals
Antibodies, Monoclonal
Blotting, Western
Body Weight
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP2B1
Cytochrome P-450 Enzyme System*
Cytochromes*
Dimethylformamide*
Humans
Hydroxylation
Immunoblotting
Injections, Intraperitoneal
Isoenzymes
Male
Microsomes
Microsomes, Liver
NADPH-Ferrihemoprotein Reductase
Olea
Oxidoreductases
Rats
Rats, Sprague-Dawley*
Olive Oil
Antibodies, Monoclonal
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP2B1
Cytochrome P-450 Enzyme System
Cytochromes
Dimethylformamide
Isoenzymes
NADPH-Ferrihemoprotein Reductase
Oxidoreductases