Genotoxic evaluation of pirfenidone using erythrocyte rodent micronucleus assay.
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.
Instituto de Biología Molecular en Medicina y Terapia Génica, Centro Universitario de Ciencias de Salud, Universidad de Guadalajara, Mexico.
Blanca E
BE
Alcántar-Díaz
Belinda C
BC
Gómez-Meda
Guillermo M
GM
Zúñiga-González
Ana L
AL
Zamora-Perez
Jaime
J
González-Cuevas
Bertha A
BA
Alvarez-Rodríguez
María Guadalupe
MG
Sánchez-Parada
Jesús J
JJ
García-Bañuelos
Juan
J
Armendáriz-Borunda
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D011247:Pregnancy; D011728:Pyridones / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009153:Mutagens; D011728:Pyridones; C093844:pirfenidone