Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12104/41733
Title: Genotoxic evaluation of pirfenidone using erythrocyte rodent micronucleus assay
Author: Mercado, M.V.-D.
García-Cobian, T.A.
Valle, J.F.M.
Torres-Carrillo, N.
Martin-Marquez, B.-T.
Arana-Argaez, V.E.
Best-Aguilera, C.R.
Martinez-García, E.-A.
Petri, M.H.
Nunez-Atahualpa, L.
Delgado-Rizo, V.
Issue Date: 2007
Abstract: Background: We describe a family with a 7-year-old proband case diagnosed with systemic lupus erythematosus (SLE) plus secondary anti-phospholipid syndrome (APS) as well as two affected paternal aunts. We compared the frequency of these polymorphisms with healthy controls. Objectives: To evaluate the mode of inheritance in this familial case of APS and SLE and the possible association of plasminogen activator inhibitor-1 (PAI-1) -675 4G/5G and PAI-2 Ser413/Cys polymorphisms. To compare the genotype frequency of these polymorphisms with the results found in a Mexican Mestizo population. Methods: PAI-1 -675 4G/5G and PAI-2 Ser413/Cys were determined by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique using Bsl I and Mwo I on four generations of the family studied. PAI-2 Ser413/Cys polymorphism was also determined in 50 healthy individuals of Mexican Mestizo origin. Results: The family pedigree demonstrated that this family did not follow a Mendelian inheritance pattern. When the PAI-2 Ser413/Cys polymorphism was examined, we found that 60% (3/5) of the relatives homozygous to Ser413/Ser were affected with SLE and/or APS (p = 0.027). The proband case was 4G/5G genotype for the PAI-1 -675 4G/5G polymorphism. No differences between healthy controls of the Mexican Mestizo population and the family studied for the PAI-2 Ser413/Cys polymorphism or PAI-1 -675 4G/5G polymorphisms were found. Conclusions: Our data indicate that this family did not follow the Mendelian inheritance pattern. The Ser413/Ser genotype demonstrated in 60% of the affected members (3/5) of this family might increase the risk for autoimmune syndromes such as APS or SLE. " 2007 Taylor & Francis on license from Scandinavian Rheumatology Research Foundation.",,,,,,"10.1080/03009740601089648",,,"http://hdl.handle.net/20.500.12104/41733","http://www.scopus.com/inward/record.url?eid=2-s2.0-34547493556&partnerID=40&md5=e7eac049d56035f38602789c05ffdbbf",,,,,,"3",,"Scandinavian Journal of Rheumatology",,"206
210",,"36",,"Scopus
WOS",,,,,,,,,,,,"Genotype Ser413/Ser of PAI-2 polymorphism Ser413/Cys is associated with anti-phospholipid syndrome and systemic lupus erythematosus in a familial case: Comparison with healthy controls",,"Article" "43508","123456789/35008",,"Alcántar-Díaz, B.E., Instituto de Biología Molecular en Medicina y Terapia Gúnica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Mexico; Gómez-Meda, B.C., Instituto de Biología Molecular en Medicina y Terapia Gúnica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Mexico; Zúñiga-González, G.M., Laboratorio de Mutagénesis, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Mexico; Zamora-Perez, A.L., Instituto de Investigación en Odontología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Mexico; González-Cuevas, J., Instituto de Biología Molecular en Medicina y Terapia Gúnica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Mexico; Álvarez-Rodríguez, B.A., Instituto de Biología Molecular en Medicina y Terapia Gúnica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Mexico; Sánchez-Parada, M.G., Instituto de Biología Molecular en Medicina y Terapia Gúnica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Mexico; García-Bañuelos, J.J., Instituto de Biología Molecular en Medicina y Terapia Gúnica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Mexico; Armendáriz-Borunda, J., Instituto de Biología Molecular en Medicina y Terapia Gúnica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Mexico, O.P.D. Hospital Civil de Guadalajara, Guadalajara, Jalisco, Mexico",,"Alcantar-Diaz, B.E.
Gomez-Meda, B.C.
Zuniga-Gonzalez, G.M.
Zamora-Perez, A.L.
Gonzalez-Cuevas, J.
Alvarez-Rodriguez, B.A.
Sanchez-Parada, M.G.
García-Banuelos, J.J.
Armendariz-Borunda, J.",,"2012",,"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. " 2012 Elsevier Ltd.
URI: http://hdl.handle.net/20.500.12104/41729
http://www.scopus.com/inward/record.url?eid=2-s2.0-84862669156&partnerID=40&md5=5b05f4cfa31adcfd0bb933a76d7151e9
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=22683486
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