Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis
Autor(a) principal: | |
---|---|
Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , |
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. |
id |
FIOCRUZ-4_f32feb8eaddcd8e24083069349ab7d7f |
---|---|
oai_identifier_str |
oai:scielo:S0074-02762011000200016 |
network_acronym_str |
FIOCRUZ-4 |
network_name_str |
Memórias do Instituto Oswaldo Cruz |
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 |
repository.mail.fl_str_mv |
|
_version_ |
1669937708917587968 |