Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol association

Autores
Miro, Maria Victoria; Rocha e Silva, Carolina; Viviani, Paula; Luque, Sonia; Lloberas, María Mercedes; Costa-Junior, Lirio; Lanusse, Carlos Edmundo; Virkel, Guillermo; Lifschitz, Adrian Luis
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The search of novel strategies for anthelmintic control is a crucial need considering the widespread increase in resistant parasitic populations in livestock. Bioactive phytochemicals may contribute to improve parasite control by enhancing the effect of existing anthelmintic drugs. The aim of the current work was to evaluate the in vivo and in vitro pharmaco-chemical interaction and the in vivo efficacy of the combination of albendazole (ABZ) with thymol (TML) in lambs naturally infected with resistant gastrointestinal nematodes. Thirty (30) lambs were allocated into three experimental groups. Each group was treated orally with either ABZ (5 mg/kg), TML (150 mg/kg, twice every 24 h) or the co-administration of both compounds. Blood samples were collected between 0 and 51 h post-treatment and TML, ABZ and its metabolites were measured by HPLC. Individual faecal samples were collected at days -1 and 14 post-treatment to perform the faecal egg count reduction test. Additionally, the effect of TML on the sulphoreduction and sulphonation of ABZ sulphoxide was assessed in vitro using ruminal content and liver microsomes, respectively. The metabolism of TML in the ruminal content was very low and the monoterpene exhibited a low degree of association with the particulate phase of the ruminal content. No changes in the pharmacokinetic behavior of ABZ sulphoxide were observed in the presence of the natural product (TML). In contrast, the ABZ sulphone Cmax and AUC were lower (P 0.002 and 0.001 respectively) in the co-administered animals (0.16 ± 0.07 μg/mL and 3.63 ± 1.21 μg.h/mL) compared with those that received ABZ alone (0.45 ± 0.15 μg/mL and 9.50 ± 2.84 μg.h/mL). TML was detected in the bloodstream between 1 and 48 h post-treatment, which indicates the time of target nematodes being exposed to the bioactive monoterpene. However, the in vivo efficacy of TML was 0% and the presence of this terpene did not increase the efficacy of ABZ. The presence of TML significantly inhibited the ruminal sulphoreduction (P 0.001) and the hepatic sulphonation (P 0.001) of ABZ sulphoxide. These observations point out that in vivo pharmaco-parasitological studies are relevant to corroborate the adverse kinetic/metabolic interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics.
EEA Balcarce
Fil: Miró, María Victoria. Universidad nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina.
Fil: Rocha e Silva, Carolina. Universidade Federal do Maranhão, Departamento de Patología; Brasil
Fil: Viviani, Paula. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; Argentina
Fil: Luque, Sonia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.
Fil: Lloberas, Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.
Fil: Costa-Junior, Livio. Universidade Federal do Maranhão, Departamento de Patología; Brasil
Fil: Lanusse, Carlos. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; Argentina
Fil: Virkel, Guillermo. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; Argentina
Fil: Lifschitz, Adrián. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; Argentina
Fuente
Veterinary Parasitology 281 : 109121 (2020)
Materia
Antihelmínticos
Timol
Cordero
Infecciones por Nematodos
Anthelmintics
Thymol
Lambs
Nematode Infections
Interacción Metabólica
Nivel de accesibilidad
acceso restringido
Condiciones de uso
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/7846

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oai_identifier_str oai:localhost:20.500.12123/7846
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network_name_str INTA Digital (INTA)
spelling Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol associationMiro, Maria VictoriaRocha e Silva, CarolinaViviani, PaulaLuque, SoniaLloberas, María MercedesCosta-Junior, LirioLanusse, Carlos EdmundoVirkel, GuillermoLifschitz, Adrian LuisAntihelmínticosTimolCorderoInfecciones por NematodosAnthelminticsThymolLambsNematode InfectionsInteracción MetabólicaThe search of novel strategies for anthelmintic control is a crucial need considering the widespread increase in resistant parasitic populations in livestock. Bioactive phytochemicals may contribute to improve parasite control by enhancing the effect of existing anthelmintic drugs. The aim of the current work was to evaluate the in vivo and in vitro pharmaco-chemical interaction and the in vivo efficacy of the combination of albendazole (ABZ) with thymol (TML) in lambs naturally infected with resistant gastrointestinal nematodes. Thirty (30) lambs were allocated into three experimental groups. Each group was treated orally with either ABZ (5 mg/kg), TML (150 mg/kg, twice every 24 h) or the co-administration of both compounds. Blood samples were collected between 0 and 51 h post-treatment and TML, ABZ and its metabolites were measured by HPLC. Individual faecal samples were collected at days -1 and 14 post-treatment to perform the faecal egg count reduction test. Additionally, the effect of TML on the sulphoreduction and sulphonation of ABZ sulphoxide was assessed in vitro using ruminal content and liver microsomes, respectively. The metabolism of TML in the ruminal content was very low and the monoterpene exhibited a low degree of association with the particulate phase of the ruminal content. No changes in the pharmacokinetic behavior of ABZ sulphoxide were observed in the presence of the natural product (TML). In contrast, the ABZ sulphone Cmax and AUC were lower (P 0.002 and 0.001 respectively) in the co-administered animals (0.16 ± 0.07 μg/mL and 3.63 ± 1.21 μg.h/mL) compared with those that received ABZ alone (0.45 ± 0.15 μg/mL and 9.50 ± 2.84 μg.h/mL). TML was detected in the bloodstream between 1 and 48 h post-treatment, which indicates the time of target nematodes being exposed to the bioactive monoterpene. However, the in vivo efficacy of TML was 0% and the presence of this terpene did not increase the efficacy of ABZ. The presence of TML significantly inhibited the ruminal sulphoreduction (P 0.001) and the hepatic sulphonation (P 0.001) of ABZ sulphoxide. These observations point out that in vivo pharmaco-parasitological studies are relevant to corroborate the adverse kinetic/metabolic interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics.EEA BalcarceFil: Miró, María Victoria. Universidad nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina.Fil: Rocha e Silva, Carolina. Universidade Federal do Maranhão, Departamento de Patología; BrasilFil: Viviani, Paula. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; ArgentinaFil: Luque, Sonia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.Fil: Lloberas, Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.Fil: Costa-Junior, Livio. Universidade Federal do Maranhão, Departamento de Patología; BrasilFil: Lanusse, Carlos. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; ArgentinaFil: Virkel, Guillermo. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; ArgentinaFil: Lifschitz, Adrián. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; ArgentinaElsevier2020-09-08T14:29:16Z2020-09-08T14:29:16Z2020-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/7846https://www.sciencedirect.com/science/article/abs/pii/S03044017203010110304-4017https://doi.org/10.1016/j.vetpar.2020.109121Veterinary Parasitology 281 : 109121 (2020)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/restrictedAccess2025-09-04T09:48:37Zoai:localhost:20.500.12123/7846instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-04 09:48:37.829INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol association
title Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol association
spellingShingle Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol association
Miro, Maria Victoria
Antihelmínticos
Timol
Cordero
Infecciones por Nematodos
Anthelmintics
Thymol
Lambs
Nematode Infections
Interacción Metabólica
title_short Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol association
title_full Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol association
title_fullStr Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol association
title_full_unstemmed Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol association
title_sort Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol association
dc.creator.none.fl_str_mv Miro, Maria Victoria
Rocha e Silva, Carolina
Viviani, Paula
Luque, Sonia
Lloberas, María Mercedes
Costa-Junior, Lirio
Lanusse, Carlos Edmundo
Virkel, Guillermo
Lifschitz, Adrian Luis
author Miro, Maria Victoria
author_facet Miro, Maria Victoria
Rocha e Silva, Carolina
Viviani, Paula
Luque, Sonia
Lloberas, María Mercedes
Costa-Junior, Lirio
Lanusse, Carlos Edmundo
Virkel, Guillermo
Lifschitz, Adrian Luis
author_role author
author2 Rocha e Silva, Carolina
Viviani, Paula
Luque, Sonia
Lloberas, María Mercedes
Costa-Junior, Lirio
Lanusse, Carlos Edmundo
Virkel, Guillermo
Lifschitz, Adrian Luis
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antihelmínticos
Timol
Cordero
Infecciones por Nematodos
Anthelmintics
Thymol
Lambs
Nematode Infections
Interacción Metabólica
topic Antihelmínticos
Timol
Cordero
Infecciones por Nematodos
Anthelmintics
Thymol
Lambs
Nematode Infections
Interacción Metabólica
dc.description.none.fl_txt_mv The search of novel strategies for anthelmintic control is a crucial need considering the widespread increase in resistant parasitic populations in livestock. Bioactive phytochemicals may contribute to improve parasite control by enhancing the effect of existing anthelmintic drugs. The aim of the current work was to evaluate the in vivo and in vitro pharmaco-chemical interaction and the in vivo efficacy of the combination of albendazole (ABZ) with thymol (TML) in lambs naturally infected with resistant gastrointestinal nematodes. Thirty (30) lambs were allocated into three experimental groups. Each group was treated orally with either ABZ (5 mg/kg), TML (150 mg/kg, twice every 24 h) or the co-administration of both compounds. Blood samples were collected between 0 and 51 h post-treatment and TML, ABZ and its metabolites were measured by HPLC. Individual faecal samples were collected at days -1 and 14 post-treatment to perform the faecal egg count reduction test. Additionally, the effect of TML on the sulphoreduction and sulphonation of ABZ sulphoxide was assessed in vitro using ruminal content and liver microsomes, respectively. The metabolism of TML in the ruminal content was very low and the monoterpene exhibited a low degree of association with the particulate phase of the ruminal content. No changes in the pharmacokinetic behavior of ABZ sulphoxide were observed in the presence of the natural product (TML). In contrast, the ABZ sulphone Cmax and AUC were lower (P 0.002 and 0.001 respectively) in the co-administered animals (0.16 ± 0.07 μg/mL and 3.63 ± 1.21 μg.h/mL) compared with those that received ABZ alone (0.45 ± 0.15 μg/mL and 9.50 ± 2.84 μg.h/mL). TML was detected in the bloodstream between 1 and 48 h post-treatment, which indicates the time of target nematodes being exposed to the bioactive monoterpene. However, the in vivo efficacy of TML was 0% and the presence of this terpene did not increase the efficacy of ABZ. The presence of TML significantly inhibited the ruminal sulphoreduction (P 0.001) and the hepatic sulphonation (P 0.001) of ABZ sulphoxide. These observations point out that in vivo pharmaco-parasitological studies are relevant to corroborate the adverse kinetic/metabolic interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics.
EEA Balcarce
Fil: Miró, María Victoria. Universidad nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina.
Fil: Rocha e Silva, Carolina. Universidade Federal do Maranhão, Departamento de Patología; Brasil
Fil: Viviani, Paula. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; Argentina
Fil: Luque, Sonia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.
Fil: Lloberas, Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.
Fil: Costa-Junior, Livio. Universidade Federal do Maranhão, Departamento de Patología; Brasil
Fil: Lanusse, Carlos. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; Argentina
Fil: Virkel, Guillermo. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; Argentina
Fil: Lifschitz, Adrián. Universidad Nacional del Centro. Facultad de Ciencias Veterinarias; Argentina
description The search of novel strategies for anthelmintic control is a crucial need considering the widespread increase in resistant parasitic populations in livestock. Bioactive phytochemicals may contribute to improve parasite control by enhancing the effect of existing anthelmintic drugs. The aim of the current work was to evaluate the in vivo and in vitro pharmaco-chemical interaction and the in vivo efficacy of the combination of albendazole (ABZ) with thymol (TML) in lambs naturally infected with resistant gastrointestinal nematodes. Thirty (30) lambs were allocated into three experimental groups. Each group was treated orally with either ABZ (5 mg/kg), TML (150 mg/kg, twice every 24 h) or the co-administration of both compounds. Blood samples were collected between 0 and 51 h post-treatment and TML, ABZ and its metabolites were measured by HPLC. Individual faecal samples were collected at days -1 and 14 post-treatment to perform the faecal egg count reduction test. Additionally, the effect of TML on the sulphoreduction and sulphonation of ABZ sulphoxide was assessed in vitro using ruminal content and liver microsomes, respectively. The metabolism of TML in the ruminal content was very low and the monoterpene exhibited a low degree of association with the particulate phase of the ruminal content. No changes in the pharmacokinetic behavior of ABZ sulphoxide were observed in the presence of the natural product (TML). In contrast, the ABZ sulphone Cmax and AUC were lower (P 0.002 and 0.001 respectively) in the co-administered animals (0.16 ± 0.07 μg/mL and 3.63 ± 1.21 μg.h/mL) compared with those that received ABZ alone (0.45 ± 0.15 μg/mL and 9.50 ± 2.84 μg.h/mL). TML was detected in the bloodstream between 1 and 48 h post-treatment, which indicates the time of target nematodes being exposed to the bioactive monoterpene. However, the in vivo efficacy of TML was 0% and the presence of this terpene did not increase the efficacy of ABZ. The presence of TML significantly inhibited the ruminal sulphoreduction (P 0.001) and the hepatic sulphonation (P 0.001) of ABZ sulphoxide. These observations point out that in vivo pharmaco-parasitological studies are relevant to corroborate the adverse kinetic/metabolic interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics.
publishDate 2020
dc.date.none.fl_str_mv 2020-09-08T14:29:16Z
2020-09-08T14:29:16Z
2020-05
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/20.500.12123/7846
https://www.sciencedirect.com/science/article/abs/pii/S0304401720301011
0304-4017
https://doi.org/10.1016/j.vetpar.2020.109121
url http://hdl.handle.net/20.500.12123/7846
https://www.sciencedirect.com/science/article/abs/pii/S0304401720301011
https://doi.org/10.1016/j.vetpar.2020.109121
identifier_str_mv 0304-4017
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
eu_rights_str_mv restrictedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Veterinary Parasitology 281 : 109121 (2020)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
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instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
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