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Evento

Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver

Ichinose, PaulaIcon ; Miró, María VictoriaIcon ; Larsen, Karen ElizabethIcon ; Lanusse, Carlos EdmundoIcon ; Lifschitz, Adrian LuisIcon ; Virkel, Guillermo LeonIcon
Tipo del evento: Congreso
Nombre del evento: American Academy of Veterinary Pharmacology and Therapeutics Special Online Student Research Symposium
Fecha del evento: 20/05/2022
Institución Organizadora: American Academy of Veterinary Pharmacology and Therapeutics;
Título del Libro: Abstracts of the American Academy of Veterinary Pharmacology and Therapeutics Special Online Student Research Symposium
Título de la revista: Acta de Resúmenes AAVPT Biennial Symposium
Editorial: American Academy of Veterinary Pharmacology and Therapeutics
Idioma: Inglés
Clasificación temática:
Otras Ciencias Veterinarias

Resumen

Fenbendazole (FBZ), a benzymidazole (BZD) drug, is used to control gastrointestinal parasites in continuous administration in swine. This drug undergoes two sequential S-oxidations through mixed function oxidases belonging to the cytochrome P450 (CYP) and flavin-monooxygenase (FMO) families. Also, BZD-containing drugs may induce the CYP1A subfamily. This work aimed to evaluate in vitro the effect of FBZ on CYP1A-dependent enzyme activities in pig liver. Five (5) piglets remained untreated (controls) and other six (6) were treated with a FBZ commercial powder mixed with food, in two dosing events repeated for 10 consecutive days, as usually is recommended. Both groups were fed ad libitum for 10 days and then euthanized for preparation of liver microsomes. FBZ and its metabolites, oxfendazole (OFZ) and fenbendazole sulphone (FBZSO2), were detected in the systemic circulation of treated piglets. Mean plasma AUCs (µg.day/mL) were 0.28±0.08 (FBZ), 4.10±0.58 (OFZ) and 4.56±1.01 (FBZSO2). Concentrations (µg/g) of FBZ, OFZ and FBZSO2 in liver parenchyma were 4.66±1.59, 3.11±1.06 and 2.30±0.99, respectively. In liver microsomes from treated animals, CYP1A-dependent enzyme activities, 7-ethoxuresorufin O-deethylase and methoxyresorufin O-demethylase, increased 24.5-fold (p=0.003) and 17.2-fold (p=0.001), respectively. The participation of the CYP pathway in the S-oxidation of FBZ into OFZ was also enhanced (3.4-fold, p=0.004) in piglets which received the anthelmintic with food (61.8±19.5 pmol/min.mg) compared to controls (18.0±6.0 pmol/min.mg). Thus, FBZ may auto-induce its own metabolism though the CYP1A pathway. This fact may also affect the fate of other xenobiotics that share the same metabolic pattern, like aflatoxin B1 present in certain pig foodstuffs.
Palabras clave: FENBENDAZOLE , METABOLISM , CYTOCHROME p450 , INDUCTION , PIG LIVER
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/225117
URL: https://cdn.ymaws.com/www.aavpt.org/resource/resmgr/proceedings/aavpt_online_stu
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Eventos(CIVETAN)
Eventos de CENTRO DE INVESTIGACION VETERINARIA DE TANDIL
Citación
Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver; American Academy of Veterinary Pharmacology and Therapeutics Special Online Student Research Symposium; Estados Unidos; 2022; 8-8
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