Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants
- Autores
- Miró, María Victoria; Costa Junior, Livio; Lloberas, Maria Mercedes; Cardozo, Patricia Alejandra; Lanusse, Carlos Edmundo; Virkel, Guillermo Leon; Lifschitz, Adrian Luis
- Año de publicación
- 2022
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- The search for novel alternatives to control gastrointestinal nematodes (GI) in ruminants is relevant in a scenario of increased anthelmintic resistance. The use of monoterpenes may enhance the effectiveness of existing synthetic anthelmintic drugs. However, it is necessary to study the potential pharmacological interactions and the fate of these compounds after their administration to ruminants. This work evaluated in vitro the effects of monoterpenes on the processes of drug metabolism and intestinal accumulation and the in vivo pharmacokinetics interactions between the best "candidate” and synthetic anthelmintics. In Phase 1, the intestinal accumulation of Rhodamine 123 (Rho123), a P-glycoprotein substrate, was studied in cattle ileum explants in the presence or absence of carvone (CNE), geraniol (GNL) and citral (CTL). The effect of CNE, GNL and CTL on flavin-containing monooxygenase (FMO) and cytochrome P450 (CYP) dependent metabolism was assessed in sheep liver microsomes measuring specific enzyme activities. The presence of CNE and GNL increased the accumulation of Rho123 in the ileum explants by 66 % and 46 % respectively (P<0.05). CNE, GNL and CIT reduced the CYP-dependent metabolism between 43 and 91 % (P<0.05) and the FMO dependent metabolism between 69 and 84 % (P<0.05). Additionally, in Phase 2, two separate experiments evaluated in vivo interaction of CNE-ivermectin (IVM) and GNL- albendazole (ABZ) in lambs. For the CNE-IVM assay, lambs were treated with either IVM (subcutaneous, 0.2 mg/kg) or IVM in combination with CNE (100 mg/kg, three oral doses every 24 h). In the GNL-ABZ trial, two experimental groups were treated with ABZ (5 mg/kg, orally) or, ABZ and GNL (100 mg/kg, two oral doses administered at -1 and 9h post-administration of ABZ) respectively. Blood samples were serially collected, and plasma levels of each compound were determined by HPLC. No undesirable effects were observed after the oral administration of CNE or GNL. In both trials, no changes were observed in the pharmacokinetic parameters of the synthetic anthelmintics after their administration combined with the monoterpenes. The highest plasma concentrations of CNE and GNL were between 3,04 and 5.27 µg/mL which are several times below the effective in vitro concentrations against GI reported in the literature. Although the presence of monoterpenes did not increase the plasma concentrations of IVM and ABZ, the lack of negative pharmacokinetic interactions gives these combinations an important pharmacological value to study their potential antiparasitic effect. The integration of in vitro and in vivo assays are critical for the design of successful alternative pharmacological tools based on the use of bioactive phytochemicals.
Fil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Costa Junior, Livio. Universidade Federal Do Maranhao.; Brasil
Fil: Lloberas, Maria Mercedes. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Cardozo, Patricia Alejandra. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Virkel, Guillermo Leon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
XXI Congresso Brasileiro de Parasitologia Veterinária
Ilheus
Brasil
Colegio Brasileiro de Parasitologia Veterinária - Materia
-
MONOTERPENES
NEMATODICIDAL
RUMINANTS
PHARMACOLOGY - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/225659
Ver los metadatos del registro completo
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Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminantsMiró, María VictoriaCosta Junior, LivioLloberas, Maria MercedesCardozo, Patricia AlejandraLanusse, Carlos EdmundoVirkel, Guillermo LeonLifschitz, Adrian LuisMONOTERPENESNEMATODICIDALRUMINANTSPHARMACOLOGYhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4The search for novel alternatives to control gastrointestinal nematodes (GI) in ruminants is relevant in a scenario of increased anthelmintic resistance. The use of monoterpenes may enhance the effectiveness of existing synthetic anthelmintic drugs. However, it is necessary to study the potential pharmacological interactions and the fate of these compounds after their administration to ruminants. This work evaluated in vitro the effects of monoterpenes on the processes of drug metabolism and intestinal accumulation and the in vivo pharmacokinetics interactions between the best "candidate” and synthetic anthelmintics. In Phase 1, the intestinal accumulation of Rhodamine 123 (Rho123), a P-glycoprotein substrate, was studied in cattle ileum explants in the presence or absence of carvone (CNE), geraniol (GNL) and citral (CTL). The effect of CNE, GNL and CTL on flavin-containing monooxygenase (FMO) and cytochrome P450 (CYP) dependent metabolism was assessed in sheep liver microsomes measuring specific enzyme activities. The presence of CNE and GNL increased the accumulation of Rho123 in the ileum explants by 66 % and 46 % respectively (P<0.05). CNE, GNL and CIT reduced the CYP-dependent metabolism between 43 and 91 % (P<0.05) and the FMO dependent metabolism between 69 and 84 % (P<0.05). Additionally, in Phase 2, two separate experiments evaluated in vivo interaction of CNE-ivermectin (IVM) and GNL- albendazole (ABZ) in lambs. For the CNE-IVM assay, lambs were treated with either IVM (subcutaneous, 0.2 mg/kg) or IVM in combination with CNE (100 mg/kg, three oral doses every 24 h). In the GNL-ABZ trial, two experimental groups were treated with ABZ (5 mg/kg, orally) or, ABZ and GNL (100 mg/kg, two oral doses administered at -1 and 9h post-administration of ABZ) respectively. Blood samples were serially collected, and plasma levels of each compound were determined by HPLC. No undesirable effects were observed after the oral administration of CNE or GNL. In both trials, no changes were observed in the pharmacokinetic parameters of the synthetic anthelmintics after their administration combined with the monoterpenes. The highest plasma concentrations of CNE and GNL were between 3,04 and 5.27 µg/mL which are several times below the effective in vitro concentrations against GI reported in the literature. Although the presence of monoterpenes did not increase the plasma concentrations of IVM and ABZ, the lack of negative pharmacokinetic interactions gives these combinations an important pharmacological value to study their potential antiparasitic effect. The integration of in vitro and in vivo assays are critical for the design of successful alternative pharmacological tools based on the use of bioactive phytochemicals.Fil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Costa Junior, Livio. Universidade Federal Do Maranhao.; BrasilFil: Lloberas, Maria Mercedes. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; ArgentinaFil: Cardozo, Patricia Alejandra. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; ArgentinaFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Virkel, Guillermo Leon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaXXI Congresso Brasileiro de Parasitologia VeterináriaIlheusBrasilColegio Brasileiro de Parasitologia VeterináriaColegio Brasileiro de Parasitologia Veterinária2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/225659Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants; XXI Congresso Brasileiro de Parasitologia Veterinária; Ilheus; Brasil; 2022; 69-69CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://cbpv.org.br/usr/arquivos/AnaisXXICBPV.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:53Zoai:ri.conicet.gov.ar:11336/225659instacron: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 09:49:54.702CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants |
| title |
Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants |
| spellingShingle |
Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants Miró, María Victoria MONOTERPENES NEMATODICIDAL RUMINANTS PHARMACOLOGY |
| title_short |
Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants |
| title_full |
Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants |
| title_fullStr |
Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants |
| title_full_unstemmed |
Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants |
| title_sort |
Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants |
| dc.creator.none.fl_str_mv |
Miró, María Victoria Costa Junior, Livio Lloberas, Maria Mercedes Cardozo, Patricia Alejandra Lanusse, Carlos Edmundo Virkel, Guillermo Leon Lifschitz, Adrian Luis |
| author |
Miró, María Victoria |
| author_facet |
Miró, María Victoria Costa Junior, Livio Lloberas, Maria Mercedes Cardozo, Patricia Alejandra Lanusse, Carlos Edmundo Virkel, Guillermo Leon Lifschitz, Adrian Luis |
| author_role |
author |
| author2 |
Costa Junior, Livio Lloberas, Maria Mercedes Cardozo, Patricia Alejandra Lanusse, Carlos Edmundo Virkel, Guillermo Leon Lifschitz, Adrian Luis |
| author2_role |
author author author author author author |
| dc.subject.none.fl_str_mv |
MONOTERPENES NEMATODICIDAL RUMINANTS PHARMACOLOGY |
| topic |
MONOTERPENES NEMATODICIDAL RUMINANTS PHARMACOLOGY |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/4.3 https://purl.org/becyt/ford/4 |
| dc.description.none.fl_txt_mv |
The search for novel alternatives to control gastrointestinal nematodes (GI) in ruminants is relevant in a scenario of increased anthelmintic resistance. The use of monoterpenes may enhance the effectiveness of existing synthetic anthelmintic drugs. However, it is necessary to study the potential pharmacological interactions and the fate of these compounds after their administration to ruminants. This work evaluated in vitro the effects of monoterpenes on the processes of drug metabolism and intestinal accumulation and the in vivo pharmacokinetics interactions between the best "candidate” and synthetic anthelmintics. In Phase 1, the intestinal accumulation of Rhodamine 123 (Rho123), a P-glycoprotein substrate, was studied in cattle ileum explants in the presence or absence of carvone (CNE), geraniol (GNL) and citral (CTL). The effect of CNE, GNL and CTL on flavin-containing monooxygenase (FMO) and cytochrome P450 (CYP) dependent metabolism was assessed in sheep liver microsomes measuring specific enzyme activities. The presence of CNE and GNL increased the accumulation of Rho123 in the ileum explants by 66 % and 46 % respectively (P<0.05). CNE, GNL and CIT reduced the CYP-dependent metabolism between 43 and 91 % (P<0.05) and the FMO dependent metabolism between 69 and 84 % (P<0.05). Additionally, in Phase 2, two separate experiments evaluated in vivo interaction of CNE-ivermectin (IVM) and GNL- albendazole (ABZ) in lambs. For the CNE-IVM assay, lambs were treated with either IVM (subcutaneous, 0.2 mg/kg) or IVM in combination with CNE (100 mg/kg, three oral doses every 24 h). In the GNL-ABZ trial, two experimental groups were treated with ABZ (5 mg/kg, orally) or, ABZ and GNL (100 mg/kg, two oral doses administered at -1 and 9h post-administration of ABZ) respectively. Blood samples were serially collected, and plasma levels of each compound were determined by HPLC. No undesirable effects were observed after the oral administration of CNE or GNL. In both trials, no changes were observed in the pharmacokinetic parameters of the synthetic anthelmintics after their administration combined with the monoterpenes. The highest plasma concentrations of CNE and GNL were between 3,04 and 5.27 µg/mL which are several times below the effective in vitro concentrations against GI reported in the literature. Although the presence of monoterpenes did not increase the plasma concentrations of IVM and ABZ, the lack of negative pharmacokinetic interactions gives these combinations an important pharmacological value to study their potential antiparasitic effect. The integration of in vitro and in vivo assays are critical for the design of successful alternative pharmacological tools based on the use of bioactive phytochemicals. Fil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina Fil: Costa Junior, Livio. Universidade Federal Do Maranhao.; Brasil Fil: Lloberas, Maria Mercedes. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina Fil: Cardozo, Patricia Alejandra. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina Fil: Virkel, Guillermo Leon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina XXI Congresso Brasileiro de Parasitologia Veterinária Ilheus Brasil Colegio Brasileiro de Parasitologia Veterinária |
| description |
The search for novel alternatives to control gastrointestinal nematodes (GI) in ruminants is relevant in a scenario of increased anthelmintic resistance. The use of monoterpenes may enhance the effectiveness of existing synthetic anthelmintic drugs. However, it is necessary to study the potential pharmacological interactions and the fate of these compounds after their administration to ruminants. This work evaluated in vitro the effects of monoterpenes on the processes of drug metabolism and intestinal accumulation and the in vivo pharmacokinetics interactions between the best "candidate” and synthetic anthelmintics. In Phase 1, the intestinal accumulation of Rhodamine 123 (Rho123), a P-glycoprotein substrate, was studied in cattle ileum explants in the presence or absence of carvone (CNE), geraniol (GNL) and citral (CTL). The effect of CNE, GNL and CTL on flavin-containing monooxygenase (FMO) and cytochrome P450 (CYP) dependent metabolism was assessed in sheep liver microsomes measuring specific enzyme activities. The presence of CNE and GNL increased the accumulation of Rho123 in the ileum explants by 66 % and 46 % respectively (P<0.05). CNE, GNL and CIT reduced the CYP-dependent metabolism between 43 and 91 % (P<0.05) and the FMO dependent metabolism between 69 and 84 % (P<0.05). Additionally, in Phase 2, two separate experiments evaluated in vivo interaction of CNE-ivermectin (IVM) and GNL- albendazole (ABZ) in lambs. For the CNE-IVM assay, lambs were treated with either IVM (subcutaneous, 0.2 mg/kg) or IVM in combination with CNE (100 mg/kg, three oral doses every 24 h). In the GNL-ABZ trial, two experimental groups were treated with ABZ (5 mg/kg, orally) or, ABZ and GNL (100 mg/kg, two oral doses administered at -1 and 9h post-administration of ABZ) respectively. Blood samples were serially collected, and plasma levels of each compound were determined by HPLC. No undesirable effects were observed after the oral administration of CNE or GNL. In both trials, no changes were observed in the pharmacokinetic parameters of the synthetic anthelmintics after their administration combined with the monoterpenes. The highest plasma concentrations of CNE and GNL were between 3,04 and 5.27 µg/mL which are several times below the effective in vitro concentrations against GI reported in the literature. Although the presence of monoterpenes did not increase the plasma concentrations of IVM and ABZ, the lack of negative pharmacokinetic interactions gives these combinations an important pharmacological value to study their potential antiparasitic effect. The integration of in vitro and in vivo assays are critical for the design of successful alternative pharmacological tools based on the use of bioactive phytochemicals. |
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2022 |
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2022 |
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http://hdl.handle.net/11336/225659 Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants; XXI Congresso Brasileiro de Parasitologia Veterinária; Ilheus; Brasil; 2022; 69-69 CONICET Digital CONICET |
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Pharmacological characterization of monoterpenes with potential nematodicidal activity in ruminants; XXI Congresso Brasileiro de Parasitologia Veterinária; Ilheus; Brasil; 2022; 69-69 CONICET Digital CONICET |
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