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

Detalhes bibliográficos
Autor(a) principal: Gotardo,Mara A
Data de Publicação: 2011
Outros Autores: Hyssa,Juliana T, Carvalho,Renato S, De-Carvalho,Rosangela R, Gueiros,Luciana S, Siqueira,Carolina M, Sarpa,Marcia, De-Oliveira,Ana Cecilia AX, Paumgartten,Francisco JR
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Memórias do Instituto Oswaldo Cruz
Texto Completo: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762011000200016
Resumo: 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.
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spelling Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasisSchistosoma mansonixenobiotic metabolismpharmacokineticscytochrome P450In 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.Instituto Oswaldo Cruz, Ministério da Saúde2011-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762011000200016Memórias do Instituto Oswaldo Cruz v.106 n.2 2011reponame:Memórias do Instituto Oswaldo Cruzinstname:Fundação Oswaldo Cruzinstacron:FIOCRUZ10.1590/S0074-02762011000200016info:eu-repo/semantics/openAccessGotardo,Mara AHyssa,Juliana TCarvalho,Renato SDe-Carvalho,Rosangela RGueiros,Luciana SSiqueira,Carolina MSarpa,MarciaDe-Oliveira,Ana Cecilia AXPaumgartten,Francisco JReng2020-04-25T17:50:57Zhttp://www.scielo.br/oai/scielo-oai.php0074-02761678-8060opendoar:null2020-04-26 02:17:32.03Memórias do Instituto Oswaldo Cruz - Fundação Oswaldo Cruztrue
dc.title.none.fl_str_mv Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis
title Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis
spellingShingle Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis
Gotardo,Mara A
Schistosoma mansoni
xenobiotic metabolism
pharmacokinetics
cytochrome P450
title_short Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis
title_full Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis
title_fullStr Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis
title_full_unstemmed Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis
title_sort Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis
author Gotardo,Mara A
author_facet Gotardo,Mara A
Hyssa,Juliana T
Carvalho,Renato S
De-Carvalho,Rosangela R
Gueiros,Luciana S
Siqueira,Carolina M
Sarpa,Marcia
De-Oliveira,Ana Cecilia AX
Paumgartten,Francisco JR
author_role author
author2 Hyssa,Juliana T
Carvalho,Renato S
De-Carvalho,Rosangela R
Gueiros,Luciana S
Siqueira,Carolina M
Sarpa,Marcia
De-Oliveira,Ana Cecilia AX
Paumgartten,Francisco JR
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Gotardo,Mara A
Hyssa,Juliana T
Carvalho,Renato S
De-Carvalho,Rosangela R
Gueiros,Luciana S
Siqueira,Carolina M
Sarpa,Marcia
De-Oliveira,Ana Cecilia AX
Paumgartten,Francisco JR
dc.subject.por.fl_str_mv Schistosoma mansoni
xenobiotic metabolism
pharmacokinetics
cytochrome P450
topic Schistosoma mansoni
xenobiotic metabolism
pharmacokinetics
cytochrome P450
dc.description.none.fl_txt_mv 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.
description 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.
publishDate 2011
dc.date.none.fl_str_mv 2011-03-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762011000200016
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762011000200016
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/S0074-02762011000200016
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Instituto Oswaldo Cruz, Ministério da Saúde
publisher.none.fl_str_mv Instituto Oswaldo Cruz, Ministério da Saúde
dc.source.none.fl_str_mv Memórias do Instituto Oswaldo Cruz v.106 n.2 2011
reponame:Memórias do Instituto Oswaldo Cruz
instname:Fundação Oswaldo Cruz
instacron:FIOCRUZ
reponame_str Memórias do Instituto Oswaldo Cruz
collection Memórias do Instituto Oswaldo Cruz
instname_str Fundação Oswaldo Cruz
instacron_str FIOCRUZ
institution FIOCRUZ
repository.name.fl_str_mv Memórias do Instituto Oswaldo Cruz - Fundação Oswaldo Cruz
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