Genotoxic evaluation of pirfenidone using erythrocyte rodent micronucleus assay

• Published in: Food and chemical toxicology 2012-08, Vol.50 (8), p.2760-2765
• Main Authors: Alcántar-Díaz, Blanca E., Gómez-Meda, Belinda C., Zúñiga-González, Guillermo M., Zamora-Perez, Ana L., González-Cuevas, Jaime, Álvarez-Rodríguez, Bertha A., Sánchez-Parada, María Guadalupe, García-Bañuelos, Jesús J., Armendáriz-Borunda, Juan
• Format: Article
• Language: English
• Subjects: adults; animal models; Animals; Anti-Inflammatory Agents, Non-Steroidal - toxicity; Antioxidant; Biological and medical sciences; cytotoxicity; DNA damage; erythrocytes; Erythrocytes - drug effects; Erythrocytes - ultrastructure; Female; Fibrosis; genotoxicity; Male; Medical sciences; Mice; Mice, Inbred BALB C; Micronuclei; Micronucleus Tests; Mutagens - toxicity; neonates; oral administration; Pregnancy; pups; Pyridone; Pyridones - toxicity; Rats; Rats, Sprague-Dawley; Rodent; Toxicology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2012.05.049

► Fibroproliferative diseases are prominent causes of morbidity and mortality worldwide and may lead to metastatic cancer. ► Pirfenidone has been proposed as an alternative treatment in various pathologies that develop fibrosis. ► The erythrocyte micronucleus assay is a simple and highly informative method that detects in vivo chromosome aberrations. ► No evidence of genotoxic or cytotoxic effects of pirfenidone were observed in two adult rodent models. ► No genotoxic effects or cytotoxicity were observed in newborn rats transplacentally exposed to pirfenidone. 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 3days, and also was administered topically to hairless Sprague Dawley rats during the final stage of gestation. Mice were sampled every 24h over the course of 6days; pregnant rats were sampled every 24h during the last 6days 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