Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study

Su, Junhui; Chang, Cui; Xiang, Qi; Zhou, Zhi-Wei; Luo, Rong; Yang, Lun; He, Zhi-Xu; Yang, Hongtu; Li, Jianan; Bei, Yu; Xu, Jinmei; Zhang, Minjing; Zhang, Qihao; Su, Zhijian; Huang, Yadong; Pang, Jiyan; Zhou, Shu-Feng

The animals were randomly divided into five groups (n=8) and treated intraperitoneally once daily with saline (blank control), soybean oil (vehicle), ketoconazole (75 mg/kg, positive control), or XKB (7 and 14 mg/kg) for 8 consecutive days. All animals had free access to standard laboratory food and water. In order to reduce the intestinal contents, animals were fasted overnight before termination of the study. Midazolam 20 mg/kg was administered orally 12 hours after the last dose of XKB. Blood samples were collected from the post ocular vein 0, 5, 15, 30, 45, 60, 90, 120, 180, 240 , 300, and 360 minutes after administration of midazolam. All blood samples were immediately centrifuged at 1,000× g for 10 minutes to obtain the plasma and stored at -20°C until further analysis. The animals were euthanized by cervical dislocation after blood collection, and liver samples were collected for further assessment of activity and expression of Cyp3a.