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
- Institución
- Instituto Nacional de Tecnología Agropecuaria
- OAI Identificador
- oai:localhost:20.500.12123/7846
Ver los metadatos del registro completo
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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) |
collection |
INTA Digital (INTA) |
instname_str |
Instituto Nacional de Tecnología Agropecuaria |
repository.name.fl_str_mv |
INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria |
repository.mail.fl_str_mv |
tripaldi.nicolas@inta.gob.ar |
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12.623145 |