Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial

Background. Diabetic foot ulcers are one disabling complication of diabetes mellitus. Pirfenidone (PFD) is a potent modulator of extracellular matrix. Modified diallyl disulfide oxide (M-DDO) is an antimicrobial and antiseptic agent. Aim. To evaluate efficacy of topical PFD + M-DDO in a randomized,...

Full description

Saved in:
Bibliographic Details
Main Authors: Luz E. Gasca-Lozano, Silvia Lucano-Landeros, Héctor Ruiz-Mercado, Adriana Salazar-Montes, Ana Sandoval-Rodríguez, Jesus Garcia-Bañuelos, Arturo Santos-Garcia, Judith R. Davila-Rodriguez, José Navarro-Partida, Hiram Bojórquez-Sepúlveda, Juan Castañeda-Gomez, José Domínguez-Rosales, Myriam A. Ruiz-Arcos, María Guadalupe Sánchez-Parada, Juan Armendariz-Borunda
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2017/3159798
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832559072394608640
author Luz E. Gasca-Lozano
Silvia Lucano-Landeros
Héctor Ruiz-Mercado
Adriana Salazar-Montes
Ana Sandoval-Rodríguez
Jesus Garcia-Bañuelos
Arturo Santos-Garcia
Judith R. Davila-Rodriguez
José Navarro-Partida
Hiram Bojórquez-Sepúlveda
Juan Castañeda-Gomez
José Domínguez-Rosales
Myriam A. Ruiz-Arcos
María Guadalupe Sánchez-Parada
Juan Armendariz-Borunda
author_facet Luz E. Gasca-Lozano
Silvia Lucano-Landeros
Héctor Ruiz-Mercado
Adriana Salazar-Montes
Ana Sandoval-Rodríguez
Jesus Garcia-Bañuelos
Arturo Santos-Garcia
Judith R. Davila-Rodriguez
José Navarro-Partida
Hiram Bojórquez-Sepúlveda
Juan Castañeda-Gomez
José Domínguez-Rosales
Myriam A. Ruiz-Arcos
María Guadalupe Sánchez-Parada
Juan Armendariz-Borunda
author_sort Luz E. Gasca-Lozano
collection DOAJ
description Background. Diabetic foot ulcers are one disabling complication of diabetes mellitus. Pirfenidone (PFD) is a potent modulator of extracellular matrix. Modified diallyl disulfide oxide (M-DDO) is an antimicrobial and antiseptic agent. Aim. To evaluate efficacy of topical PFD + M-DDO in a randomized, double-blind trial versus ketanserin in the treatment of noninfected chronic DFU. Methods. Patients received PFD + M-DDO or ketanserin for 6 months. Relative ulcer volume (RUV) was measured every month; biopsies were taken at baseline and months 1 and 2 for histopathology and gene expression analysis for COL-1α, COL-4, KGF, VEGF, ACTA2 (α-SMA), elastin, fibronectin, TGF-β1, TGF-β3, HIF-1α, and HIF-1β. Results. Reduction of median RUV in the PFD + M-DDO group was 62%, 89.8%, and 99.7% at months 1–3 and 100% from months 4 to 6. Ketanserin reduced RUV in 38.4%, 56%, 60.8%, 94%, 94.8%, and 100% from the first to the sixth month, respectively. Healing score improved 4.5 points with PFD + M-DDO and 1.5 points with ketanserin compared to basal value. Histology analysis revealed few inflammatory cells and organized/ordered collagen fiber bundles in PFD + M-DDO. Expression of most genes was increased with PFD + M-DDO; 43.8% of ulcers were resolved using PFD + M-DDO and 23.5% with ketanserin. Conclusion. PFD + M-DDO was more effective than ketanserin in RUV reduction.
format Article
id doaj-art-52f4e94276d44b019a934d87e7e40784
institution Kabale University
issn 2314-6745
2314-6753
language English
publishDate 2017-01-01
publisher Wiley
record_format Article
series Journal of Diabetes Research
spelling doaj-art-52f4e94276d44b019a934d87e7e407842025-02-03T01:30:56ZengWileyJournal of Diabetes Research2314-67452314-67532017-01-01201710.1155/2017/31597983159798Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled TrialLuz E. Gasca-Lozano0Silvia Lucano-Landeros1Héctor Ruiz-Mercado2Adriana Salazar-Montes3Ana Sandoval-Rodríguez4Jesus Garcia-Bañuelos5Arturo Santos-Garcia6Judith R. Davila-Rodriguez7José Navarro-Partida8Hiram Bojórquez-Sepúlveda9Juan Castañeda-Gomez10José Domínguez-Rosales11Myriam A. Ruiz-Arcos12María Guadalupe Sánchez-Parada13Juan Armendariz-Borunda14Institute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoRegional Hospital Dr. Valentín Gómez Farías ISSSTE, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoTecnologico de Monterrey, Campus Guadalajara, Jalisco, MexicoHospital Civil de Guadalajara, Guadalajara, JAL, MexicoTecnologico de Monterrey, Campus Guadalajara, Jalisco, MexicoHospital Civil de Guadalajara, Guadalajara, JAL, MexicoHospital Civil de Guadalajara, Guadalajara, JAL, MexicoInstitute of Chronic-Degenerative Diseases, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoInstitute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, MexicoBackground. Diabetic foot ulcers are one disabling complication of diabetes mellitus. Pirfenidone (PFD) is a potent modulator of extracellular matrix. Modified diallyl disulfide oxide (M-DDO) is an antimicrobial and antiseptic agent. Aim. To evaluate efficacy of topical PFD + M-DDO in a randomized, double-blind trial versus ketanserin in the treatment of noninfected chronic DFU. Methods. Patients received PFD + M-DDO or ketanserin for 6 months. Relative ulcer volume (RUV) was measured every month; biopsies were taken at baseline and months 1 and 2 for histopathology and gene expression analysis for COL-1α, COL-4, KGF, VEGF, ACTA2 (α-SMA), elastin, fibronectin, TGF-β1, TGF-β3, HIF-1α, and HIF-1β. Results. Reduction of median RUV in the PFD + M-DDO group was 62%, 89.8%, and 99.7% at months 1–3 and 100% from months 4 to 6. Ketanserin reduced RUV in 38.4%, 56%, 60.8%, 94%, 94.8%, and 100% from the first to the sixth month, respectively. Healing score improved 4.5 points with PFD + M-DDO and 1.5 points with ketanserin compared to basal value. Histology analysis revealed few inflammatory cells and organized/ordered collagen fiber bundles in PFD + M-DDO. Expression of most genes was increased with PFD + M-DDO; 43.8% of ulcers were resolved using PFD + M-DDO and 23.5% with ketanserin. Conclusion. PFD + M-DDO was more effective than ketanserin in RUV reduction.http://dx.doi.org/10.1155/2017/3159798
spellingShingle Luz E. Gasca-Lozano
Silvia Lucano-Landeros
Héctor Ruiz-Mercado
Adriana Salazar-Montes
Ana Sandoval-Rodríguez
Jesus Garcia-Bañuelos
Arturo Santos-Garcia
Judith R. Davila-Rodriguez
José Navarro-Partida
Hiram Bojórquez-Sepúlveda
Juan Castañeda-Gomez
José Domínguez-Rosales
Myriam A. Ruiz-Arcos
María Guadalupe Sánchez-Parada
Juan Armendariz-Borunda
Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial
Journal of Diabetes Research
title Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial
title_full Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial
title_fullStr Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial
title_full_unstemmed Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial
title_short Pirfenidone Accelerates Wound Healing in Chronic Diabetic Foot Ulcers: A Randomized, Double-Blind Controlled Trial
title_sort pirfenidone accelerates wound healing in chronic diabetic foot ulcers a randomized double blind controlled trial
url http://dx.doi.org/10.1155/2017/3159798
work_keys_str_mv AT luzegascalozano pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT silvialucanolanderos pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT hectorruizmercado pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT adrianasalazarmontes pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT anasandovalrodriguez pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT jesusgarciabanuelos pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT arturosantosgarcia pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT judithrdavilarodriguez pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT josenavarropartida pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT hirambojorquezsepulveda pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT juancastanedagomez pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT josedominguezrosales pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT myriamaruizarcos pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT mariaguadalupesanchezparada pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial
AT juanarmendarizborunda pirfenidoneaccelerateswoundhealinginchronicdiabeticfootulcersarandomizeddoubleblindcontrolledtrial