Effect of 1-benzylimidazole on cytochromes P-450 induction and on the activities of epoxide hydrolases and UDP-glucuronosyltransferases in rat liver

Effect of 4-(4-Chlorobenzyl)pyridine on Rat Hepatic Microsomal Cytochrome P450 and Drug-Metabolizing Enzymes in Vivo and in Vitro.

“…Magdalou et al have shown that 1-benzylimidazole fails to displace benzo[a]pyrene from the Ah-receptor; however, they suggest that the compound could bind to the receptor with low efficiency. 9) These findings, [9][10][11] together with our present data (Fig. 3, Table 1), suggest that a halogenated benzyl moiety would be an indispensable structure for the induction of CYP2B1, as well as steric hindrance due to the halogen atoms, which could not take a coplanarity.…”

“…1) Many investigators have demonstrated that N-substituted imidazole-containing drugs and chemicals, such as clotrimazole and 1-benzylimidazole, are potent inducers of rat hepatic P450 and its associated mono-oxygenase activities. [2][3][4][5][6][7][8][9] To date, we have reported that compounds substituted at the 1-or 4-position of the imidazole-and pyridine-rings, respectively, are potent inducers of rat hepatic microsomal P450 in vivo, but these chemicals markedly inhibited P450-dependent mono-oxygenase activity when added in an in vitro assay system. [10][11][12][13][14] Recently, we reported that 2,2Ј-dipyridyl ketone induces both P450 and heme oxygenase activity, whereas 2,2Ј-dipyridyl and 2,2Ј-dipyridyl amine are able to increase heme oxygenase activity with a decreasing P450 content.…”

Induction potential of fluconazole toward drug-metabolizing enzymes in rats

“…Itraconazole is distributed into the cellular membranes, decreasing the probability of interaction with such a receptor. Binding to a cytosolic receptor has been implicated for inducers belonging to the polycyclic hydrocarbon (25) and pregnenolone-16a-carbonitrile (36) families but also in the induction by 1-benzylimidazole (20). Induction of cytochrome P-450C by the latter compound involved the binding to a receptor with only low efficiency.…”

“…Tioconazole, on the other hand, preferentially induced UDP-glucuronosyltransferase activity towards 4-nitrophenol (33). Clotrimazole was classified as a mixed-type inducer, displaying characteristics of both the P-450IlB (phenobarbital-inducible) and P-450111 (pregnenolone-16a-carbonitrile-inducible) families of cytochrome P-450 inducers (34,35), whereas 1-benzylimidazole exhibited both polycyclic aromatic hydrocarbon-and phenobarbital-type induction (20,30). In the present study, it is shown that the triazole fluconazole also behaves as a mixed-type inducer that strongly induced N,N-dimethylaniline N-demethylase activity, preferentially induced by phenobarbital (Table 1), as well as p-nitroanisole O-demethylase activity, preferentially induced by 3-methylcholanthrene (Table-1).…”

Induction of CYP1A by the N‐imidazole derivative, 1‐benzylimidazole

“…1), is an inducer of CYP1A in rainbow trout liver cells and to generate initial data on the mechanism of CYP1A induction by this N ‐imidazole derivative. Benzylimidazole was selected because it was reported to be a CYP1A inducer in rats, showing structural differences from prototype CYP1A inducers, such as β‐naphthoflavone (βNF) [9], and being not able to displace benzo[α]pyrene from the AhR in rat hepatocytes [19]. The concentration‐dependent effect of BIM on CYP1A catalytic activity, measured as EROD activity, and on CYP1A mRNA, estimated by reverse transcriptase‐polymerase chain reaction (RT‐PCR), was studied in cultured rainbow trout hepatocytes.…”