Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats

Autores
Perdomo, Virginia; Rigalli, Juan Pablo; Villanueva, Silvina Stella Maris; Ruiz, Maria Laura; Luquita, Marcelo Gabriel; Echenique, Claudia G.; Catania, Viviana Alicia
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The effect of antichagasic benznidazole (BZL; 100mg/kg body weight/day, 3 consecutive days, intraperitoneally) on biotransfor-mation systems and ABC transporters was evaluated in rats. Expression of cytochrome P-450 (CYP3A), UDP-glucuronosyltrans-ferase (UGT1A), glutathioneS-transferases (alpha glutathioneS-transferase [GST-], GST-, andGST-), multidrug-resis-tance-associated protein 2 (Mrp2), and P glycoprotein (P-gp) in liver, small intestine, and kidney was estimated by Western blotting. Increases in hepatic CYP3A (30%) andGST-(40%) and in intestinal GST-(72% in jejunumand 136% in ileum) were detected. Significant increases in Mrp2 (300%) and P-gp (500%) proteins in liver from BZL-treated rats were observedwithout changes in kidney. P-gp and Mrp2 were also increased by BZL in jejunum (170%and 120%, respectively). In ileum, only P-gp was increased by BZL (50%). The activities of GST, P-gp, and Mrp2 correlatedwell with the upregulation of proteins in liver and jejunum. Plasma decay of a test dose of BZL (5mg/kg body weight) administered intraduodenally was faster (295%) and the area under the concentration-time curve (AUC) was lower (41%) for BZL-pretreated rats than for controls. The biliary excretion of BZLwas higher (60%) in the BZL group, and urinary excretion of BZL did not showdifferences between groups. The amount of absorbed BZL in intestinal sacs was lower (25%) in pretreated rats than in controls. In conclusion, induction of biotransforma-tion enzymes and/or transporters by BZL could increase the clearance and/or decrease the intestinal absorption of coadminis-tered drugs that are substrates of these systems, including BZL itself.
Fil: Perdomo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Rigalli, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Villanueva, Silvina Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Ruiz, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Luquita, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Echenique, Claudia G.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Catania, Viviana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Materia
Benznidazol
Biotransformation
Abc Transporters
Rats
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/6105
Acceder
id CONICETDig_9b00d8840e37a958d141694b71130545
oai_identifier_str oai:ri.conicet.gov.ar:11336/6105
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in RatsPerdomo, VirginiaRigalli, Juan PabloVillanueva, Silvina Stella MarisRuiz, Maria LauraLuquita, Marcelo GabrielEchenique, Claudia G.Catania, Viviana AliciaBenznidazolBiotransformationAbc TransportersRatshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The effect of antichagasic benznidazole (BZL; 100mg/kg body weight/day, 3 consecutive days, intraperitoneally) on biotransfor-mation systems and ABC transporters was evaluated in rats. Expression of cytochrome P-450 (CYP3A), UDP-glucuronosyltrans-ferase (UGT1A), glutathioneS-transferases (alpha glutathioneS-transferase [GST-], GST-, andGST-), multidrug-resis-tance-associated protein 2 (Mrp2), and P glycoprotein (P-gp) in liver, small intestine, and kidney was estimated by Western blotting. Increases in hepatic CYP3A (30%) andGST-(40%) and in intestinal GST-(72% in jejunumand 136% in ileum) were detected. Significant increases in Mrp2 (300%) and P-gp (500%) proteins in liver from BZL-treated rats were observedwithout changes in kidney. P-gp and Mrp2 were also increased by BZL in jejunum (170%and 120%, respectively). In ileum, only P-gp was increased by BZL (50%). The activities of GST, P-gp, and Mrp2 correlatedwell with the upregulation of proteins in liver and jejunum. Plasma decay of a test dose of BZL (5mg/kg body weight) administered intraduodenally was faster (295%) and the area under the concentration-time curve (AUC) was lower (41%) for BZL-pretreated rats than for controls. The biliary excretion of BZLwas higher (60%) in the BZL group, and urinary excretion of BZL did not showdifferences between groups. The amount of absorbed BZL in intestinal sacs was lower (25%) in pretreated rats than in controls. In conclusion, induction of biotransforma-tion enzymes and/or transporters by BZL could increase the clearance and/or decrease the intestinal absorption of coadminis-tered drugs that are substrates of these systems, including BZL itself.Fil: Perdomo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Rigalli, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Villanueva, Silvina Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Ruiz, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Luquita, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Echenique, Claudia G.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Catania, Viviana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaAmerican Society for Microbiology2013-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/mswordapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdftext/htmlhttp://hdl.handle.net/11336/6105Perdomo, Virginia; Rigalli, Juan Pablo; Villanueva, Silvina Stella Maris; Ruiz, Maria Laura; Luquita, Marcelo Gabriel; et al.; Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 57; 10; 10-2013; 4894-49020066-4804enginfo:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/57/10/4894.fullinfo:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.02531-12info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:31Zoai:ri.conicet.gov.ar:11336/6105instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:56:31.508CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats
title Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats
spellingShingle Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats
Perdomo, Virginia
Benznidazol
Biotransformation
Abc Transporters
Rats
title_short Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats
title_full Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats
title_fullStr Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats
title_full_unstemmed Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats
title_sort Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats
dc.creator.none.fl_str_mv Perdomo, Virginia
Rigalli, Juan Pablo
Villanueva, Silvina Stella Maris
Ruiz, Maria Laura
Luquita, Marcelo Gabriel
Echenique, Claudia G.
Catania, Viviana Alicia
author Perdomo, Virginia
author_facet Perdomo, Virginia
Rigalli, Juan Pablo
Villanueva, Silvina Stella Maris
Ruiz, Maria Laura
Luquita, Marcelo Gabriel
Echenique, Claudia G.
Catania, Viviana Alicia
author_role author
author2 Rigalli, Juan Pablo
Villanueva, Silvina Stella Maris
Ruiz, Maria Laura
Luquita, Marcelo Gabriel
Echenique, Claudia G.
Catania, Viviana Alicia
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Benznidazol
Biotransformation
Abc Transporters
Rats
topic Benznidazol
Biotransformation
Abc Transporters
Rats
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The effect of antichagasic benznidazole (BZL; 100mg/kg body weight/day, 3 consecutive days, intraperitoneally) on biotransfor-mation systems and ABC transporters was evaluated in rats. Expression of cytochrome P-450 (CYP3A), UDP-glucuronosyltrans-ferase (UGT1A), glutathioneS-transferases (alpha glutathioneS-transferase [GST-], GST-, andGST-), multidrug-resis-tance-associated protein 2 (Mrp2), and P glycoprotein (P-gp) in liver, small intestine, and kidney was estimated by Western blotting. Increases in hepatic CYP3A (30%) andGST-(40%) and in intestinal GST-(72% in jejunumand 136% in ileum) were detected. Significant increases in Mrp2 (300%) and P-gp (500%) proteins in liver from BZL-treated rats were observedwithout changes in kidney. P-gp and Mrp2 were also increased by BZL in jejunum (170%and 120%, respectively). In ileum, only P-gp was increased by BZL (50%). The activities of GST, P-gp, and Mrp2 correlatedwell with the upregulation of proteins in liver and jejunum. Plasma decay of a test dose of BZL (5mg/kg body weight) administered intraduodenally was faster (295%) and the area under the concentration-time curve (AUC) was lower (41%) for BZL-pretreated rats than for controls. The biliary excretion of BZLwas higher (60%) in the BZL group, and urinary excretion of BZL did not showdifferences between groups. The amount of absorbed BZL in intestinal sacs was lower (25%) in pretreated rats than in controls. In conclusion, induction of biotransforma-tion enzymes and/or transporters by BZL could increase the clearance and/or decrease the intestinal absorption of coadminis-tered drugs that are substrates of these systems, including BZL itself.
Fil: Perdomo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Rigalli, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Villanueva, Silvina Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Ruiz, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Luquita, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Echenique, Claudia G.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Catania, Viviana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
description The effect of antichagasic benznidazole (BZL; 100mg/kg body weight/day, 3 consecutive days, intraperitoneally) on biotransfor-mation systems and ABC transporters was evaluated in rats. Expression of cytochrome P-450 (CYP3A), UDP-glucuronosyltrans-ferase (UGT1A), glutathioneS-transferases (alpha glutathioneS-transferase [GST-], GST-, andGST-), multidrug-resis-tance-associated protein 2 (Mrp2), and P glycoprotein (P-gp) in liver, small intestine, and kidney was estimated by Western blotting. Increases in hepatic CYP3A (30%) andGST-(40%) and in intestinal GST-(72% in jejunumand 136% in ileum) were detected. Significant increases in Mrp2 (300%) and P-gp (500%) proteins in liver from BZL-treated rats were observedwithout changes in kidney. P-gp and Mrp2 were also increased by BZL in jejunum (170%and 120%, respectively). In ileum, only P-gp was increased by BZL (50%). The activities of GST, P-gp, and Mrp2 correlatedwell with the upregulation of proteins in liver and jejunum. Plasma decay of a test dose of BZL (5mg/kg body weight) administered intraduodenally was faster (295%) and the area under the concentration-time curve (AUC) was lower (41%) for BZL-pretreated rats than for controls. The biliary excretion of BZLwas higher (60%) in the BZL group, and urinary excretion of BZL did not showdifferences between groups. The amount of absorbed BZL in intestinal sacs was lower (25%) in pretreated rats than in controls. In conclusion, induction of biotransforma-tion enzymes and/or transporters by BZL could increase the clearance and/or decrease the intestinal absorption of coadminis-tered drugs that are substrates of these systems, including BZL itself.
publishDate 2013
dc.date.none.fl_str_mv 2013-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/6105
Perdomo, Virginia; Rigalli, Juan Pablo; Villanueva, Silvina Stella Maris; Ruiz, Maria Laura; Luquita, Marcelo Gabriel; et al.; Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 57; 10; 10-2013; 4894-4902
0066-4804
url http://hdl.handle.net/11336/6105
identifier_str_mv Perdomo, Virginia; Rigalli, Juan Pablo; Villanueva, Silvina Stella Maris; Ruiz, Maria Laura; Luquita, Marcelo Gabriel; et al.; Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 57; 10; 10-2013; 4894-4902
0066-4804
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/57/10/4894.full
info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.02531-12
info:eu-repo/semantics/altIdentifier/doi/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/msword
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
text/html
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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