The Multifaceted Role of Pirfenidone and Its Novel Targets

Overview

Journal Fibrogenesis Tissue Repair

Publisher Biomed Central

Date 2010 Sep 3

PMID 20809935

Citations 63

Authors

Jose Macias-Barragan

Ana Sandoval-Rodriguez

Jose Navarro-Partida

Juan Armendariz-Borunda

Affiliations

Soon will be listed here.

Abstract

Background: Pirfenidone (PFD) is a molecule that exhibits antifibrotic properties in a variety of in vitro and animal models of lung, liver and renal fibrosis. These pathologies share many fibrogenic pathways with an abnormal fibrous wound-healing process; consequently, tissue repair and tissue regeneration-regulating mechanisms are altered.

Objective: To investigate the usefulness of PFD as an antifibrotic agent in clinical and experimental models of fibrotic disease.

Conclusions: There is a growing understanding of the molecular effects of PFD on the wound healing mechanism, leading to novel approaches for the management of fibrosis in lung, liver and renal tissues. Although the optimum treatment for fibrosis remains undefined, it is possible that combined therapeutic regimens that include this wide-application molecule, pirfenidone, could offer a useful treatment for fibrotic disease.

Citing Articles

Pirfenidone-induced liver injury, a case report of a rare idiosyncratic reaction.

Fortunati F, Froidure A, Baldin P, Horsmans Y, Lanthier N, Dahlqvist G Ther Adv Drug Saf. 2024; 15:20420986241270866.

PMID: 39286238 PMC: 11403680. DOI: 10.1177/20420986241270866.

Implant-based breast surgery and capsular formation: when, how and why?-a narrative review.

Gorgy A, Barone N, Nepon H, Dalfen J, Efanov J, Davison P Ann Transl Med. 2023; 11(11):385.

PMID: 37970601 PMC: 10632565. DOI: 10.21037/atm-23-131.

Sarcoidosis-associated pulmonary fibrosis: joining the dots.

Bandyopadhyay D, Mirsaeidi M Eur Respir Rev. 2023; 32(169).

PMID: 37758275 PMC: 10523156. DOI: 10.1183/16000617.0085-2023.

A Soft Skin Adhesive (SSA) Patch for Extended Release of Pirfenidone in Burn Wounds.

Chung E, Nguyen J, Tellkamp-Schehr T, Goebel K, Ollek A, Krein C Pharmaceutics. 2023; 15(7).

PMID: 37514029 PMC: 10386754. DOI: 10.3390/pharmaceutics15071842.

Pirfenidone Protects from UVB-Induced Photodamage in Hairless Mice.

Martinez-Alvarado Y, Amezcua-Galvez E, Davila-Rodriguez J, Sandoval-Rodriguez A, Galicia-Moreno M, Almeida-Lopez M Molecules. 2023; 28(7).

PMID: 37049691 PMC: 10096127. DOI: 10.3390/molecules28072929.

References

Mei S, Yao W, Zhu Y, Zhao J . Protection of pirfenidone against an early phase of oleic acid-induced acute lung injury in rats. J Pharmacol Exp Ther. 2004; 313(1):379-88. DOI: 10.1124/jpet.104.078030. View

Zia S, Hyde D, Giri S . Development of a bleomycin hamster model of subchronic lung fibrosis. Pathology. 1992; 24(3):155-63. DOI: 10.3109/00313029209063164. View

Boigk G, Stroedter L, Herbst H, WALDSCHMIDT J, Riecken E, Schuppan D . Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats. Hepatology. 1997; 26(3):643-9. DOI: 10.1002/hep.510260316. View

Kehrer J, Margolin S . Pirfenidone diminishes cyclophosphamide-induced lung fibrosis in mice. Toxicol Lett. 1997; 90(2-3):125-32. DOI: 10.1016/s0378-4274(96)03845-3. View

Salazar-Montes A, Ruiz-Corro L, Lopez-Reyes A, Castrejon-Gomez E, Armendariz-Borunda J . Potent antioxidant role of pirfenidone in experimental cirrhosis. Eur J Pharmacol. 2008; 595(1-3):69-77. DOI: 10.1016/j.ejphar.2008.06.110. View

Garcia L, Hernandez I, Sandoval A, Salazar A, Garcia J, Vera J . Pirfenidone effectively reverses experimental liver fibrosis. J Hepatol. 2002; 37(6):797-805. DOI: 10.1016/s0168-8278(02)00272-6. View

Liu H, Drew P, Cheng Y, Visner G . Pirfenidone inhibits inflammatory responses and ameliorates allograft injury in a rat lung transplant model. J Thorac Cardiovasc Surg. 2005; 130(3):852-8. DOI: 10.1016/j.jtcvs.2005.04.012. View

Grattendick K, Nakashima J, Feng L, Giri S, Margolin S . Effects of three anti-TNF-alpha drugs: etanercept, infliximab and pirfenidone on release of TNF-alpha in medium and TNF-alpha associated with the cell in vitro. Int Immunopharmacol. 2008; 8(5):679-87. DOI: 10.1016/j.intimp.2008.01.013. View

Park H, Bao L, Kim Y, Cho I, Lee C, Hyun B . Pirfenidone suppressed the development of glomerulosclerosis in the FGS/Kist mouse. J Korean Med Sci. 2003; 18(4):527-33. PMC: 3055080. DOI: 10.3346/jkms.2003.18.4.527. View

10.

Shihab F, Bennett W, Yi H, Andoh T . Effect of pirfenidone on apoptosis-regulatory genes in chronic cyclosporine nephrotoxicity. Transplantation. 2005; 79(4):419-26. DOI: 10.1097/01.tp.0000151721.99418.48. View

11.

Liu H, Drew P, Gaugler A, Cheng Y, Visner G . Pirfenidone inhibits lung allograft fibrosis through L-arginine-arginase pathway. Am J Transplant. 2005; 5(6):1256-63. DOI: 10.1111/j.1600-6143.2005.00876.x. View

12.

DePaso W, WINTERBAUER R . Interstitial lung disease. Dis Mon. 1991; 37(2):61-133. View

13.

Bedossa P, Houglum K, Trautwein C, Holstege A, Chojkier M . Stimulation of collagen alpha 1(I) gene expression is associated with lipid peroxidation in hepatocellular injury: a link to tissue fibrosis?. Hepatology. 1994; 19(5):1262-71. View

14.

Poli G, Parola M . Oxidative damage and fibrogenesis. Free Radic Biol Med. 1997; 22(1-2):287-305. DOI: 10.1016/s0891-5849(96)00327-9. View

15.

Novo E, Parola M . Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis Tissue Repair. 2008; 1(1):5. PMC: 2584013. DOI: 10.1186/1755-1536-1-5. View

16.

Poulin Braim A, MacDonald M, Bruss M, Stanley S, Giri J, Giri S . Pharmacokinetics and clinical effects of pirfenidone administered intravenously in horses. Am J Vet Res. 2008; 69(7):952-60. DOI: 10.2460/ajvr.69.7.952. View

17.

Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K . Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2005; 171(9):1040-7. DOI: 10.1164/rccm.200404-571OC. View

18.

Gancedo M, Ruiz-Corro L, Salazar-Montes A, Rincon A, Armendariz-Borunda J . Pirfenidone prevents capsular contracture after mammary implantation. Aesthetic Plast Surg. 2007; 32(1):32-40. DOI: 10.1007/s00266-007-9051-4. View

19.

Parola M, ROBINO G . Oxidative stress-related molecules and liver fibrosis. J Hepatol. 2001; 35(2):297-306. DOI: 10.1016/s0168-8278(01)00142-8. View

20.

Visner G, Liu F, Bizargity P, Liu H, Liu K, Yang J . Pirfenidone inhibits T-cell activation, proliferation, cytokine and chemokine production, and host alloresponses. Transplantation. 2009; 88(3):330-8. PMC: 2726969. DOI: 10.1097/TP.0b013e3181ae3392. View