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

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

Autor Feitoza, Carla Q. Autor UNIFESP Google Scholar
Gonalves, Giselle M. Autor UNIFESP Google Scholar
Semedo, Patricia Autor UNIFESP Google Scholar
Cenedeze, Marcos A. Autor UNIFESP Google Scholar
Pinheiro, Helady S. Google Scholar
Beraldo, Felipe Caetano Google Scholar
Santos, Oscar Fernando Pavao dos Autor UNIFESP Google Scholar
Teixeira, Vicente de Paula A. Google Scholar
Reis, Marlene A. dos Google Scholar
Mazzali, Marilda Google Scholar
Pacheco-Silva, Alvaro Autor UNIFESP Google Scholar
Camara, Niels O. S. Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Univ Fed Juiz de Fora
Universidade Estadual de Campinas (UNICAMP)
Univ Fed Triangulo Mineiro
Universidade de São Paulo (USP)
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.
Idioma Inglês
Financiador Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundacao de Amparo a Pesquisa of São Paulo
Número do financiamento Fundacao de Amparo a Pesquisa of São Paulo: 04/08311-4
Fundacao de Amparo a Pesquisa of São Paulo: 04/13449-7
Fundacao de Amparo a Pesquisa of São Paulo: 06/03982-5
Fundacao de Amparo a Pesquisa of São Paulo: 07/07139-3
Data 2008-11-01
Publicado em Molecular Medicine. Manhasset: Feinstein Inst Med Res, v. 14, n. 11-12, p. 724-730, 2008.
ISSN 1076-1551 (Sherpa/Romeo, fator de impacto)
Editor Feinstein Inst Med Res
Extensão 724-730
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000260980300008

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