Por favor, use este identificador para citar o enlazar este ítem:
DOI: 10.14670/HH-11-712
Twittear
Título: | Protective function of pirfenidone and everolimus on the development of chronic allograft rejection after experimental lung transplantation |
Fecha de publicación: | 2016 |
Editorial: | Universidad de Murcia. Departamento de Biología Celular e Histología |
Cita bibliográfica: | Histology and histopathology, Vol.31, nº7 (2016) |
ISSN: | 1699-5848 0213-3911 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología |
Palabras clave: | Lung transplantation Rat Chronic rejection Pirfenidone Everolimus |
Resumen: | Long-term survival of lung allografts is limited by chronic rejection (CR). Oxidative stress (OxS) plays a central role in the development of CR. We investigated the influence of pirfenidone (alone or in combination with everolimus) on OxS and CR. A rat model of left lung allo-transplantation (F344- to-WKY) was used to evaluate the effects of pirfenidone alone [0,85% in chow from postoperative day (POD) -3 to 20/60] and in combination with everolimus [2,5 mg/kg bw daily from POD 7 to 20/60]. Allografts of non-treated animals, everolimus treated animals and right, non-transplanted lungs were used as references. Immunohistology of myeloperoxidase (MPO), haemoxygenase-1 (HO-1), iron and platelet-derivedgrowth-factor-receptor-alpha (PDGFR-a) were performed. On POD 20, all groups showed severe acute rejection (ISHLT A3-4/B1R-B2R). Groups treated with pirfenidone showed a lower interstitial inflammatory infiltration and a lower participation of highly fibrotic degenerated vessels (ISHLT-D2R). In the long term follow up (POD 60), pirfenidone alone significantly reduced chronic airway rejection (ISHLT-C; p≤0.05), interstitial fibrosis (IF; p≤0.05), content of collagen (p≤0.05), expression of PDGFR-a (p≤0.05) and the deposition of iron (p≤0.05). All groups treated with pirfenidone showed a high expression of the cytoprotective enzyme HO-1 (p≤0.05). The additional application of everolimus resulted in a significant decrease of chronic airway rejection (ISHLT-C; p≤0.05), vasculopathy (ISHLT; p≤0.05) and IF (p≤0.05). In conclusion, early application of pirfenidone inhibited the progression of CR by its anti-fibrotic and anti-oxidative properties. The additional application of an m-TOR-inhibitor increased the anti-fibrotic effects of pirfenidone which resulted in a reduction of CR after experimental LTx. |
Autor/es principal/es: | Suesskind-Schwendi, M. von Heige, E. l Pfaehler, S. Haneya, A. Schmid, C. Hirt, S.W. Lehle, K. |
URI: | http://hdl.handle.net/10201/111421 |
DOI: | DOI: 10.14670/HH-11-712 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 13 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Aparece en las colecciones: | Vol.31, nº7 (2016) |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
Suesskind-Schwendi-31-793-805-2016.pdf | 5,4 MB | Adobe PDF | Visualizar/Abrir |
Este ítem está sujeto a una licencia Creative Commons Licencia Creative Commons