Chen Bingbing, Pan Peipei, Wang Li, Chen Menchun, Dong Yaoyao, Ge Ren-Shan, Hu Guo-Xin
School of Pharmacy, Wenzhou Medical University, Wenzhou, China.
Pharmacology. 2015;95(3-4):145-53. doi: 10.1159/000380883. Epub 2015 Mar 31.
Cytochrome P450 (CYP) enzymes are involved in the metabolism of endogenous and exogenous compounds. Human and rat liver microsomes were used to investigate the inhibitory effects of methoxychlor (MXC) and its metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on the activities of corresponding human and rat CYPs. Probe drugs were used to test the inhibitory effects of MXC and HPTE on human and rat CYPs. The results showed that MXC and HPTE inhibited both human CYP2C9 and rat liver CYP2C11 activity, with half-maximal inhibitory concentration (IC50) values of 15.47 ± 0.36 (MXC) and 8.87 ± 0.53 μmol/l (HPTE) for human CYP2C9, and of 22.45 ± 1.48 (MXC) and 24.63 ± 1.35 μmol/l (HPTE) for rat CYP2C11. MXC and HPTE had no effects on human CYP2C19 activity but inhibited rat CYP2C6 activity with IC50 values of 14.84 ± 0.04 (MXC) and 8.72 ± 0.25 μmol/l (HPTE). With regard to human CYP2D6 and rat CYP2D2 activity, only HPTE potently inhibited human CYP2D6 activity, with an IC50 value of 16.56 ± 0.69 μmol/l. Both chemicals had no effect on human CYP3A4 and rat CYP3A1 activity. In summary, MXC and HPTE are potent inhibitors of some human and rat CYPs.
细胞色素P450（CYP）酶参与内源性和外源性化合物的代谢。使用人和大鼠肝微粒体研究甲氧滴滴涕（MXC）及其代谢物2,2-双（对羟基苯基）-1,1,1-三氯乙烷（HPTE）对相应人和大鼠CYP活性的抑制作用。使用探针药物测试MXC和HPTE对人和大鼠CYP的抑制作用。结果表明，MXC和HPTE均抑制人CYP2C9和大鼠肝CYP2C11活性，人CYP2C9的半数最大抑制浓度（IC50）值分别为15.47±0.36（MXC）和8.87±0.53μmol/L（HPTE），大鼠CYP2C11的IC50值分别为22.45±1.48（MXC）和24.63±1.35μmol/L（HPTE）。MXC和HPTE对人CYP2C19活性无影响，但抑制大鼠CYP2C6活性，IC50值分别为14.84±0.04（MXC）和8.72±0.25μmol/L（HPTE）。关于人CYP2D6和大鼠CYP2D2活性，只有HPTE能有效抑制人CYP2D6活性，IC50值为16.56±0.69μmol/L。两种化学物质对人CYP3A4和大鼠CYP3A1活性均无影响。总之，MXC和HPTE是一些人和大鼠CYP的强效抑制剂。
