Evaluation of MTBH, a novel hesperetin derivative, on the activity of hepatic cytochrome P450 isoform in vitro and in vivo using a cocktail method by HPLC-MS/MS

Autor: Jie Wang, Haijun Dong, Shuai Song, Tianci Zhang Mr., Yan Qin Miss, Sheng Wang, Wei Wang, Yilong Zhang, Jun Li Prof., Jiayin Sun Miss, Yuru Fan, Xiaohui Huang, Guanjun Chen, Chenlin Shen
Rok vydání: 2021
Předmět:
Zdroj: Xenobiotica. 51:1389-1399
ISSN: 1366-5928
0049-8254
Popis: 8-methylene-tert-butylamine-3',5,7-trihydroxy-4'-methoxyflavanone (MTBH), a novel hesperidin derivative, has potential in the prevention of hepatic disease, however, its effects on cytochrome P450 isoforms (P450s) remains unexplored. The purpose was to investigate the effects of MTBH on the mRNA, protein levels and activities of six P450s (1A2, 2C11/9, 2D2/6, 3A1/4, 2C13/19 and 2E1) in vitro and in vivo.In vitro study, rat and human liver microsomes were adopted to elucidate the inhibitory effect of MTBH on six P450s using probe drugs. In vivo study, Sprague-Dawley male rats were treated with MTBH (25, 50 or 100 mg/kg for 28 consecutive days), phenobarbital (80 mg/kg for 12 consecutive days) or 0.5% CMC-Na solution (control group) by intragastric administration, then, the mRNA, protein levels and activities of liver P450s were analyzed by real-time PCR, western blotting and probe-drug incubation systems, respectively.The in vitro study indicated that MTBH inhibits the activities of CYP3A1/4 and CYP2E1 in rat and human liver microsomes. In vivo data showed that MTBH inhibits mRNA, protein levels and activities of CYP3A1 and CYP2E1 in medium- and high-dose MTBH groups.MTBH has the potential to cause drug-drug interactions when co-administered with drugs that are metabolized by CYP3A1/4 and CYP2E1.
Databáze: OpenAIRE
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