Genotoxic evaluation of pirfenidone using erythrocyte rodent micronucleus assay

被引:9
作者
Alcantar-Diaz, Blanca E. [1 ]
Gomez-Meda, Belinda C. [1 ]
Zuniga-Gonzalez, Guillermo M. [2 ]
Zamora-Perez, Ana L. [3 ]
Gonzalez-Cuevas, Jaime [1 ]
Alvarez-Rodriguez, Bertha A. [1 ]
Guadalupe Sanchez-Parada, Maria [1 ]
Garcia-Banuelos, Jesus J. [1 ]
Armendariz-Borunda, Juan [1 ,4 ]
机构
[1] Univ Guadalajara, Inst Biol Mol Med & Terapia Gen, Ctr Univ Ciencias Salud, Guadalajara 44340, Jalisco, Mexico
[2] Inst Mexicano Seguro Social, Lab Mutagenesis, Ctr Invest Biomed Occidente, Mexico City, DF, Mexico
[3] Univ Guadalajara, Inst Invest Odontol, Ctr Univ Ciencias Salud, Guadalajara 44340, Jalisco, Mexico
[4] OPD Hosp Civil Guadalajara, Guadalajara, Jalisco, Mexico
关键词
DNA damage; Micronuclei; Fibrosis; Antioxidant; Pyridone; Rodent; FOLATE SUPPLEMENTATION; ANTIFIBROTIC AGENT; PERIPHERAL-BLOOD; INDUCTION; PHARMACOKINETICS; THERAPIES;
D O I
10.1016/j.fct.2012.05.049
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
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. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2760 / 2765
页数:6
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