Modulation of inflammatory response by selective inhibition of cyclooxygenase-1 and cyclooxygenase-2 in acute kidney injury

Modulation of inflammatory response by selective inhibition of cyclooxygenase-1 and cyclooxygenase-2 in acute kidney injury

Autor Feitoza, Carla Q. Autor UNIFESP Google Scholar
Semedo, Patricia Autor UNIFESP Google Scholar
Goncalves, Giselle M. Autor UNIFESP Google Scholar
Cenedeze, Marcos A. Autor UNIFESP Google Scholar
Pinheiro, Helady S. Google Scholar
Pavao dos Santos, Oscar Fernando Autor UNIFESP Google Scholar
Landgraf, Richardt Gama Autor UNIFESP Google Scholar
Pacheco-Silva, Alvaro Autor UNIFESP Google Scholar
Saraiva Camara, Niels Olsen Autor UNIFESP Google Scholar
Instituição Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Univ Fed Juiz de Fora
Hosp Israelita Albert Einstein
Resumo This work explored the role of inhibition of cyclooxygenases (COXs) in modulating the inflammatory response triggered by acute kidney injury.C57Bl/6 mice were used.Animals were treated or not with indomethacin (IMT) prior to injury (days -1 and 0).Animals were subjected to 45 min of renal pedicle occlusion and sacrificed at 24 h after reperfusion. Serum creatinine and blood urea nitrogen, reactive oxygen species (ROS), kidney myeloperoxidase (MPO) activity, and prostaglandin E2 (PGE(2)) levels were analyzed. Tumor necrosis factor (TNF)-alpha, t-bet, interleukin (IL)-10, IL-1 beta, heme oxygenase (HO)-1, and prostaglandin E synthase (PGES) messenger RNA (mRNA) were studied. Cytokines were quantified in serum.IMT-treated animals presented better renal function with less acute tubular necrosis and reduced ROS and MPO production. Moreover, the treatment was associated with lower expression of TNF-alpha, PGE(2), PGES, and t-bet and upregulation of HO-1 and IL-10. This profile was mirrored in serum, where inhibition of COXs significantly decreased interferon (IFN)-gamma, TNF-alpha, and IL-12 p70 and upregulated IL-10.COXs seem to play an important role in renal ischemia and reperfusion injury, involving the secretion of pro-inflammatory cytokines, activation of neutrophils, and ROS production. Inhibition of COX pathway is intrinsically involved with cytoprotection.
Assunto Cyclooxygenase
Renal ischemia and reperfusion injury
Cytokines
Heme oxygenase 1
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento FAPESP: 04/08311-4
FAPESP: 07/07139-3 e 06/03982-5
Data 2010-03-01
Publicado em Inflammation Research. Basel: Birkhauser Verlag Ag, v. 59, n. 3, p. 167-175, 2010.
ISSN 1023-3830 (Sherpa/Romeo, fator de impacto)
Editor Birkhauser Verlag Ag
Extensão 167-175
Fonte http://dx.doi.org/10.1007/s00011-009-0083-x
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000274331800001
URI http://repositorio.unifesp.br/handle/11600/32316

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