Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2017 (2017), Article ID 3159798, 12 pages
https://doi.org/10.1155/2017/3159798
Clinical Study

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

1Institute for Molecular Biology and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, JAL, Mexico
2Regional Hospital Dr. Valentín Gómez Farías ISSSTE, Guadalajara, JAL, Mexico
3Tecnologico de Monterrey, Campus Guadalajara, Jalisco, Mexico
4Hospital Civil de Guadalajara, Guadalajara, JAL, Mexico
5Institute of Chronic-Degenerative Diseases, CUCS, University of Guadalajara, Guadalajara, JAL, Mexico

Correspondence should be addressed to Juan Armendariz-Borunda

Received 25 July 2017; Revised 16 November 2017; Accepted 3 December 2017; Published 31 December 2017

Academic Editor: Mark Yorek

Copyright © 2017 Luz E. Gasca-Lozano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. International Diabetes Federation, 2015, http://www.diabetesatlas.org.
  2. P. Zhang, J. Lu, Y. Jing, S. Tang, D. Zhu, and Y. Bi, “Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis,” Annals of Medicine, vol. 49, no. 2, pp. 106–116, 2016. View at Publisher · View at Google Scholar · View at Scopus
  3. D. Martins-Mendes, M. Monteiro-Soares, E. J. Boyko et al., “The independent contribution of diabetic foot ulcer on lower extremity amputation and mortality risk,” Journal of Diabetes and its Complications, vol. 28, no. 5, pp. 632–638, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. G. E. Reiber, E. J. Boyko, and D. G. Smith, “Lower extremity foot ulcers and amputations in diabetes,” in Diabetes in America, M. I. Harris and M. P. Stern, Eds., pp. 409–428, U.S. Government Printing Office, Bethesda, MD, USA, 1995. View at Google Scholar
  5. L. V. Fortington, J. H. B. Geertzen, J. J. van Netten, K. Postema, G. M. Rommers, and P. U. Dijkstra, “Short and long term mortality rates after a lower limb amputation,” European Journal of Vascular and Endovascular Surgery, vol. 46, no. 1, pp. 124–131, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. K. Jörgens, S. J. Stoll, J. Pohl et al., “High tissue glucose alters intersomitic blood vessels in zebrafish via methylglyoxal targeting the VEGF receptor signaling cascade,” Diabetes, vol. 64, no. 1, pp. 213–225, 2015. View at Publisher · View at Google Scholar · View at Scopus
  7. S. Yamano, W. P. Kuo, and C. Sukotjo, “Downregulated gene expression of TGF-βs in diabetic oral wound healing,” Journal of Cranio-Maxillo-Facial Surgery, vol. 41, no. 2, pp. e42–e48, 2013. View at Publisher · View at Google Scholar · View at Scopus
  8. H. El Gazaerly, D. M. Elbardisey, H. M. Eltokhy, and D. Teaama, “Effect of transforming growth factor beta 1 on wound healing in induced diabetic rats,” International Journal of Health Sciences, vol. 7, no. 2, pp. 160–172, 2013. View at Publisher · View at Google Scholar
  9. K. A. Mace, D. H. Yu, K. Z. Paydar, N. Boudreau, and D. M. Young, “Sustained expression of Hif-1α in the diabetic environment promotes angiogenesis and cutaneous wound repair,” Wound Repair and Regeneration, vol. 15, no. 5, pp. 636–645, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. M. F. Siqueira, J. Li, L. Chehab et al., “Impaired wound healing in mouse models of diabetes is mediated by TNF-α dysregulation and associated with enhanced activation of forkhead box O1 (FOXO1),” Diabetologia, vol. 53, no. 2, pp. 378–388, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. S. Werner, M. Breeden, G. Hübner, D. G. Greenhalgh, and M. T. Longaker, “Induction of keratinocyte growth factor expression is reduced and delayed during wound healing in the genetically diabetic mouse,” The Journal of Investigative Dermatology, vol. 103, no. 4, pp. 469–473, 1994. View at Publisher · View at Google Scholar
  12. H. Brem and M. Tomic-Canic, “Cellular and molecular basis of wound healing in diabetes,” The Journal of Clinical Investigation, vol. 117, no. 5, pp. 1219–1222, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. A. Desmoulière, A. Geinoz, F. Gabbiani, and G. Gabbiani, “Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts,” The Journal of Cell Biology, vol. 122, no. 1, pp. 103–111, 1993. View at Publisher · View at Google Scholar
  14. S. Hata, K. Okamura, M. Hatta, H. Ishikawa, and J. Yamazaki, “Proteolytic and non-proteolytic activation of keratinocyte-derived latent TGF-β1 induces fibroblast differentiation in a wound-healing model using rat skin,” Journal of Pharmacological Sciences, vol. 124, no. 2, pp. 230–243, 2014. View at Publisher · View at Google Scholar · View at Scopus
  15. T. C. Alba-Loureiro, C. D. Munhoz, J. O. Martins et al., “Neutrophil function and metabolism in individuals with diabetes mellitus,” Brazilian Journal of Medical and Biological Research, vol. 40, no. 8, pp. 1037–1044, 2007. View at Publisher · View at Google Scholar
  16. B. Ponugoti, G. Dong, and D. T. Graves, “Role of forkhead transcription factors in diabetes-induced oxidative stress,” Experimental Diabetes Research, vol. 2012, Article ID 939751, 7 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Janka-Zires, P. Almeda-Valdes, A. C. Uribe-Wiechers et al., “Topical administration of pirfenidone increases healing of chronic diabetic foot ulcers: a randomized crossover study,” Journal of Diabetes Research, vol. 2016, Article ID 7340641, 7 pages, 2016. View at Publisher · View at Google Scholar · View at Scopus
  18. P. W. Noble, C. Albera, W. Z. Bradford et al., “Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials,” The European Respiratory Journal, vol. 47, no. 1, pp. 243–253, 2016. View at Publisher · View at Google Scholar · View at Scopus
  19. E. Conte, E. Gili, E. Fagone, M. Fruciano, M. Iemmolo, and C. Vancheri, “Effect of pirfenidone on proliferation, TGF-β-induced myofibroblast differentiation and fibrogenic activity of primary human lung fibroblasts,” European Journal of Pharmaceutical Sciences, vol. 58, pp. 13–19, 2014. View at Publisher · View at Google Scholar · View at Scopus
  20. K. J. Grattendick, J. M. Nakashima, L. Feng, S. N. Giri, and S. B. Margolin, “Effects of three anti-TNF-α drugs: etanercept, infliximab and pirfenidone on release of TNF-α in medium and TNF-α associated with the cell in vitro,” International Immunopharmacology, vol. 8, no. 5, pp. 679–687, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. S. N. Giri, S. N. Giri, S. Leonard, X. Shi, S. B. Margolin, and V. Vallyathan, “Effects of pirfenidone on the generation of reactive oxygen species in vitro,” Journal of Environmental Pathology, Toxicology and Oncology, vol. 18, no. 3, pp. 169–177, 1999. View at Google Scholar
  22. P. K. Mandapalli, S. Labala, J. Bojja, and V. V. K. Venuganti, “Effect of pirfenidone delivered using layer-by-layer thin film on excisional wound healing,” European Journal of Pharmaceutical Sciences, vol. 83, pp. 166–174, 2016. View at Publisher · View at Google Scholar · View at Scopus
  23. J. Apelqvist, K. Bakker, W. H. van Houtum, N. C. Schaper, and on behalf of the International Working Group on the Diabetic Foot (IWGDF) Editorial Board, “Practical guidelines on the management and prevention of the diabetic foot: based upon the International Consensus on the Diabetic Foot (2007) prepared by the International Working Group on the Diabetic Foot,” Diabetes/Metabolism Research and Reviews, vol. 24, no. S1, pp. S181–S187, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. Cofepris, “Comisión de Autorización Sanitaria, Dirección Ejecutiva de Autorización de Productos y Establecimientos. Certificados de Libre Venta Expedidos 2013,” 2013, http://www.cofepris.gob.mx/AS/Documents/RegistroSanitarioMedicamentos/CLV%C2%B4s%20Aprobados%202013.xls.pdf.
  25. National Center for Biotechnology Information, “PubChem Compound Database. CID=3822,” 2017, https://pubchem.ncbi.nlm.nih.gov/compound/3822.
  26. P. A. J. Janssen, H. Janssen, G. Cauwenbergh et al., “Use of topical ketanserin in the treatment of skin ulcers: a double-blind study,” Journal of the American Academy of Dermatology, vol. 21, no. 1, pp. 85–90, 1989. View at Publisher · View at Google Scholar
  27. J. Apelqvist, J. Castenfors, J. Larsson, A. Stenström, and G. Persson, “Ketanserin in the treatment of diabetic foot ulcer with severe peripheral vascular disease,” International Angiology, vol. 9, no. 2, pp. 120–124, 1990. View at Google Scholar
  28. F. R. Martínez-de Jesús, M. Morales-Guzmán, M. Castañeda, A. Pérez-Morales, J. García-Alonso, and I. Mendiola-Segura, “Randomized single-blind trial of topical ketanserin for healing acceleration of diabetic foot ulcers,” Archives of Medical Research, vol. 28, no. 1, pp. 95–99, 1997. View at Google Scholar
  29. P. Quatresooz, M. Kharfi, P. Paquet, V. Vroome, G. Cauwenbergh, and G. E. Pierard, “Healing effect of ketanserin on chronic leg ulcers in patients with diabetes,” Journal of the European Academy of Dermatology and Venereology, vol. 20, no. 3, pp. 277–281, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. FDA Wound Healing Clinical Focus Group, “Guidance for industry: chronic cutaneous ulcer and burn wounds—developing products for treatment,” Wound Repair and Regeneration, vol. 9, no. 4, pp. 258–268, 2001. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Gupta and P. Kumar, “Assessment of the histological state of the healing wound,” Plastic and Aesthetic Research, vol. 2, no. 5, p. 239, 2015. View at Publisher · View at Google Scholar
  32. P. Chomczynski and N. Sacchi, “Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction,” Analytical Biochemistry, vol. 162, no. 1, pp. 156–159, 1987. View at Publisher · View at Google Scholar · View at Scopus
  33. “Applied Byosistem,” http://www6.appliedbiosystems.com/support/tutorials/pdf/performing_rq_gene_exp_rtpcr.pdf.
  34. W. H. Herman, R. Pop-Busui, B. H. Braffett et al., “Use of the Michigan Neuropathy Screening Instrument as a measure of distal symmetrical peripheral neuropathy in type 1 diabetes: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications,” Diabetic Medicine, vol. 29, no. 7, pp. 937–944, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. Z. Bayhan, S. Zeren, F. E. Kocak et al., “Antiadhesive and anti-inflammatory effects of pirfenidone in postoperative intra-abdominal adhesion in an experimental rat model,” The Journal of Surgical Research, vol. 201, no. 2, pp. 348–355, 2016. View at Publisher · View at Google Scholar · View at Scopus
  36. S. Patel, A. Maheshwari, and A. Chandra, “Biomarkers for wound healing and their evaluation,” Journal of Wound Care, vol. 25, no. 1, pp. 46–55, 2016. View at Publisher · View at Google Scholar · View at Scopus
  37. D. G. Armstrong, L. A. Lavery, and L. B. Harkless, “Validation of a diabetic wound classification system: the contribution of depth, infection, and ischemia to risk of amputation,” Diabetes Care, vol. 21, no. 5, pp. 855–859, 1998. View at Publisher · View at Google Scholar · View at Scopus
  38. T. Yen, D. Thao, and T. Thuoc, “An overview on keratinocyte growth factor: from the molecular properties to clinical applications,” Protein and Peptide Letters, vol. 21, no. 3, pp. 306–317, 2014. View at Publisher · View at Google Scholar
  39. M. Takeo, W. Lee, and M. Ito, “Wound healing and skin regeneration,” Cold Spring Harbor Perspectives in Medicine, vol. 5, no. 1, article a023267, 2015. View at Publisher · View at Google Scholar · View at Scopus
  40. D. Nowak, A. Popow-Woźniak, L. Raźnikiewicz, and M. Malicka-Błaszkiewicz, “Actin in the wound healing process,” Postepy Biochemii, vol. 55, no. 2, pp. 138–144, 2009. View at Google Scholar
  41. V. Viswanathan and S. Kumpatla, “Pattern and causes of amputation in diabetic patients—a multicentric study from India,” The Journal of the Association of Physicians of India, vol. 59, pp. 148–151, 2011. View at Google Scholar