Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis

Memórias do Instituto Oswaldo Cruz

Mara A Gotardo¹  Juliana T Hyssa¹  Renato S Carvalho¹  Rosangela R De-carvalho¹  Luciana S Gueiros¹  Carolina M Siqueira¹  Marcia Sarpa¹  Ana Cecilia Ax De-oliveira¹  Francisco Jr Paumgartten¹ 

[1] ,Fundação Oswaldo Cruz Escola Nacional de Saúde Pública Departamento de Ciências BiológicasRio de Janeiro RJ ,Brasil

关键词: Schistosoma mansoni;    xenobiotic metabolism;    pharmacokinetics;    cytochrome P450;   

DOI  :  10.1590/S0074-02762011000200016

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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