RESUMEN
Objective: To study the effect of arecoline hydrobromide (AH) on rat hepatic CYP2B expression/activity, as well as the underlying regulation mechanism in vivo. Methods: After oral administration of AH (4, 20, and 100 mg/kg/d) to rats for 7 consecutive days, the hepatic CYP2B activity was detected by LC-MS/MS method, the protein levels of hepatic CYP2B, total CAR, and endonuclear CAR were detected by Western blotting, and the hepatic CYP2B1 mRNA level was detected by real-time PCR. Results: AH treatment had no effect on rat hepatic CYP2B protein level, but the hepatic CYP2B1 mRNA level was dose-dependently increased. Additionally, although the hepatic CYP2B activity was induced by AH treatment, the induction was weakened with the dose increase of AH. Furthermore, the protein content of hepatic endonuclear CAR was increased while the total CAR protein remained unchanged following AH treatment. Conclusion: AH induces rat hepatic CYP2B by promoting nuclear translocation of CAR. The regulation of AH on rat hepatic CYP2B largely involve transcriptional activation of the gene, partially involve the post-translational modification of CYP2B protein. Our results also suggest that the risk of metabolic interaction could be existed when the substrate drugs of CYP2B are administered in betel-quid used human.