Genotoxic evaluation of pirfenidone using erythrocyte rodent micronucleus assay |
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Authors: | Blanca E. Alcá ntar-Dí az,Belinda C. Gó mez-Meda,Guillermo M. Zú ñ iga-Gonzá lez,Ana L. Zamora-Perez,Jaime Gonzá lez-Cuevas,Bertha A. Á lvarez-Rodrí guez,Marí a Guadalupe Sá nchez-Parada,Jesú s J. Garcí a-Bañ uelos,Juan Armendá riz-Borunda |
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Affiliation: | 1. Instituto de Biología Molecular en Medicina y Terapia Génica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Mexico;2. Laboratorio de Mutagénesis, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Mexico;3. Instituto de Investigación en Odontología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Mexico;4. O.P.D. Hospital Civil de Guadalajara, Guadalajara, Jalisco, Mexico |
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Abstract: | Pirfenidone is a non-steroidal antifibrotic compound that has been proposed in clinical protocols and experimental studies as a pharmacological treatment for fibroproliferative diseases. The objective of this study was to determine the genotoxicity or cytotoxicity of three doses of pirfenidone using the micronuclei test in peripheral blood erythrocytes of rodent models. Pirfenidone was administered orally to Balb-C mice for 3 days, and also was administered topically to hairless Sprague Dawley rats during the final stage of gestation. Mice were sampled every 24 h over the course of 6 days; pregnant rats were sampled every 24 h during the last 6 days of gestation, and pups were sampled at birth. Blood smears were analyzed and the frequencies of micronucleated erythrocytes (MNEs), micronucleated polychromatic erythrocytes (MNPCEs), and the proportion of polychromatic erythrocytes (PCEs), were recorded in samples from mice, pregnant rats and rat neonates. Increases in MN frequencies (p < 0.03) were noted only in the positive control groups. No genotoxic effects or decreased PCE values were observed neither in newborn rats transplacentally exposed to pirfenidone, or in two adult rodent models when pirfenidone was administered orally or topically. |
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Keywords: | DNA damage Micronuclei Fibrosis Antioxidant Pyridone Rodent |
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