Inhibition of COX 1 and 2 prior to Renal Ischemia/Reperfusion Injury Decreases the Development of Fibrosis

Autor(es):Mostrar menos -

Feitoza, Carla Q. ^[1] ; Gonalves, Giselle M. ^[1] ; Semedo, Patricia ^[1] ; Cenedeze, Marcos A. ^[1] ; Pinheiro, Helady S. ^{[2, 3]} ; Beraldo, Felipe Caetano ; dos Santos, Oscar Fernando Pavao ^[1] ; Teixeira, Vicente de Paula A. ; dos Reis, Marlene A. ; Mazzali, Marilda ; Pacheco-Silva, Alvaro ^[1] ; Camara, Niels O. S. ^{[1, 4]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Div Nephrol, Expt & Clin Immunol Lab, Sao Paulo - Brazil

^[2] Univ Fed Triangulo Mineiro, Uberaba, MG - Brazil

^[3] Univ Fed Juiz de Fora, Div Nephrol, Juiz De Fora, MG - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Transplantat Immunobiol Lab, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Medicine; v. 14, n. 11-12, p. 724-730, NOV-DEC 2008.
• Citações Web of Science: 41

Resumo

Ischemia and reperfusion injury (IRI) contributes to the development of chronic interstitial fibrosis/tubular atrophy in renal allograft patients, Cyclooxygenase (COX) 1 and 2 actively participate in acute ischemic injury by activating endothelial cells and inducing oxidative stress. Furthermore, blockade of COX I and 2 has been associated with organ improvement after ischemic damage. The aim of this study was to evaluate the role of COX I and 2 in the development of fibrosis by performing a COX I and 2 blockade immediately before IRI We subjected C57BI/6 male mice to 60 min of unilateral renal pedicle occlusion, Prior to surgery mice were either treated with indomethacin (IMT) at days -1 and 0 or were untreated. Blood and kidney samples were collected 6 wks after IRI. Kidney samples were analyzed by real-time reverse transcription-poly me rase chain reaction for expression of transforming growth factor beta (TGF-beta), monocyte chemoattractant protein 1 (MCP-1), osteopontin (OPN), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1 beta, IL-10, heme oxygenose 1 (HO-1), vimentin, connective-tissue growth factor (CTGF), collagen 1, and bone morphogenic protein 7 (BMP-7), To assess tissue fibrosis we performed morphometric analyses and Sirius red staining. We also performed immunohistochemical analysis of anti-actin smooth muscle, Renal function did not significantly differ between groups. Animals pretreated with IMT showed significantly less interstitial fibrosis than nontreated animals. Gene transcript analyses showed decreased expression of TGF-beta, MCP-1,TNF-alpha, IL-1-beta, vimentin, collagen 1, CTGF and IL-10 mRNA (all P < 0.05), Moreover, HO-I mRNA was increased in animals pretreated with IMT (P < 0.05) Conversely, IMT treatment decreased osteopontin expression and enhanced BMP-7 expression, although these levels did rot reach statistical significance when compared with control expression levels, I he blockade of COX 1 and 2 resulted in less tissue fibrosis, which was associated with a decrease in proinflammatory cytokines and enhancement of the protective cellular response. (AU)

• Processo FAPESP: 04/13449-7 - O papel da heme oxigenase-1 (ho-1) na melhora da lesao renal induzida por isquemia/reperfusao apos bloqueio das cicloxigenases (cox) 1 e 2.
• Beneficiário: Carla Quarim Feitoza
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 06/03982-5 - Aspectos moleculares envolvidos na atividade microbicida e inflamatória de leucócitos no pulmão
• Beneficiário: Sônia Jancar
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 07/07139-3 - Investigando o papel da heme-oxigenase 1 em diferentes processos inflamatórios renais em modelos animais
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático