title: Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis.
abstract: In this study, we investigated the expression and activity of liver cytochrome P450s (CYPs) and praziquantel (PZQ) kinetics in mice infected with Schistosoma mansoni. Swiss Webster (SW) mice of both genders were infected (100 cercariae) on postnatal day 10 and killed on post-infection days (PIDs) 30 or 55. Non-infected mice of the same age and sex served as controls. Regardless of mouse sex, infection depressed the activities of CYP1A [ethoxy/methoxy-resorufin-O-dealkylases (EROD/MROD)], 2B9/10 [pentoxy/benzyloxy-resorufin-O-dealkylases (PROD, BROD)], 2E1 [p-nitrophenol-hydroxylase (PNPH)] and 3A11 [erythromycin N-demethylase (END)] on PID 55 but not on PID 30. On PID 55, infection decreased liver CYP mRNA levels (real-time reverse transcription-polymerase chain reaction). On PID 30, whereas mRNA levels remained unaltered in males, they were depressed in females. Plasma PZQ (200 and 400 mg/kg body weight intraperitoneally) levels were measured (high-performance liquid chromatography) at different post-treatment intervals. In males and females, infection delayed the PZQ clearance on PID 55, but not on PID 30. Therefore, it can be concluded that schistosomiasis down-modulated CYP expression and activity and delayed PZQ clearance on PID 55, when a great number of parasite eggs were lodged in the liver. On PID 30, when egg-laying was initiated by the worms, no change of CYP expression and activity was found, except for a depression of CYP1A2 and 3A11 mRNAs in female mice.
authors.affiliation: Departamento de Ciências Biológicas, Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil.
authors.forename: Mara A
authors.initials: MA
authors.lastname: Gotardo
authors.forename: Juliana T
authors.initials: JT
authors.lastname: Hyssa
authors.forename: Renato S
authors.initials: RS
authors.lastname: Carvalho
authors.forename: Rosangela R
authors.initials: RR
authors.lastname: De-Carvalho
authors.forename: Luciana S
authors.initials: LS
authors.lastname: Gueiros
authors.forename: Carolina M
authors.initials: CM
authors.lastname: Siqueira
authors.forename: Marcia
authors.initials: M
authors.lastname: Sarpa
authors.forename: Ana Cecilia A X
authors.initials: AC
authors.lastname: De-Oliveira
authors.forename: Francisco
authors.initials: F
authors.lastname: Paumgartten
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D011223:Praziquantel / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism
chemical_list: D000871:Anthelmintics; D012333:RNA, Messenger; D011223:Praziquantel; D003577:Cytochrome P-450 Enzyme System