Study on induction of rat liver cytochrome P450 enzymes by bencycloquidium bromide
- Author:
Lu-Ning SUN
1
Author Information
- Publication Type:Journal Article
- Keywords: Bencycloquidium bromide; CYP450; Induction; Probe substrates method; Rat liver microsome
- From: Chinese Pharmaceutical Journal 2013;48(17):1454-1459
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To study the induction effect of bencycloquidium bromide (BCQB) on rat liver cytochrome P450 enzymes. METHODS: Rats were divided into solvent control group, positive control (phenobarbital) group and BCQB group. The rats in BCQB groups were intranasally administered with 1, 3, and 9 mg · kg-1 BCQB, respectively. After multiple-dose administration, the rats were sacrificed, and the livers were weighed and prepared to microsomes. Then the liver coefficients were calculated, and the total content of CYP450 enzymes in liver microsomes was determined by spectrophotometer. HPLC-MS/MS method was adopted and validated to simultaneously determine the productive velocity of 6β-hydroxyl testosterone and paracetamol after incubation of rat liver microsomes. The activities of CYP1A1/2 and CYP3A1/2 were measured according to the productive velocity. RESULTS: The liver coefficients, total content of CYP450 enzymes, and activity of CYP1A1/2 were significantly different (P<0.05) between solvent control group and positive control group, while comparable (P>0.05) between solvent control group and BCQB groups. The activity of CYP3A1/2 in BCQB groups was not higher than solvent control group. CONCLUSION: Phenobarbital has induction effect on rat liver CYP450 enzymes. The test system can be used to evaluate the induction effect of BCQB on rat liver CYP450 enzymes. BCQB has no induction effect on liver CYP450 enzymes in rats.
