title: Effects of methoxychlor and 2,2-bis ( p -hydroxyphenyl)-1,1,1-trichloroethane on cytochrome P450 enzyme activities in human and rat livers.
abstract: 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.
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou, China.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Chen
authors.forename: Peipei
authors.initials: P
authors.lastname: Pan
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Menchun
authors.initials: M
authors.lastname: Chen
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Dong
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Hu
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008731:Methoxychlor / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley
chemical_list: D007306:Insecticides; D010636:Phenols; D003577:Cytochrome P-450 Enzyme System; C404910:2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane; D008731:Methoxychlor