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


Autoria(s): FEITOZA, Carla Q.; SEMEDO, Patricia; GONCALVES, Giselle M.; CENEDEZE, Marcos A.; PINHEIRO, Helady S.; SANTOS, Oscar Fernando Pavao dos; LANDGRAF, Richardt Gama; PACHECO-SILVA, Alvaro; CAMARA, Niels Olsen Saraiva
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

20/10/2012

20/10/2012

2010

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.

Brazilian Foundation-FAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo)[04/08311-4]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Brazilian Foundation-FAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo)[07/07139-3 e 06/03982-5]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

CNPq

Identificador

INFLAMMATION RESEARCH, v.59, n.3, p.167-175, 2010

1023-3830

http://producao.usp.br/handle/BDPI/28279

10.1007/s00011-009-0083-x

http://dx.doi.org/10.1007/s00011-009-0083-x

Idioma(s)

eng

Publicador

BIRKHAUSER VERLAG AG

Relação

Inflammation Research

Direitos

restrictedAccess

Copyright BIRKHAUSER VERLAG AG

Palavras-Chave #Cyclooxygenase #Renal ischemia and reperfusion injury #Cytokines #Heme oxygenase 1 #ISCHEMIA-REPERFUSION INJURY #ACUTE-RENAL-FAILURE #NF-KAPPA-B #HEPATIC ISCHEMIA/REPERFUSION INJURY #FOCAL CEREBRAL-ISCHEMIA #TNF-ALPHA #EPITHELIAL-CELLS #NITRIC-OXIDE #ANTIINFLAMMATORY DRUGS #NEUTROPHIL RECRUITMENT #Cell Biology #Immunology
Tipo

article

original article

publishedVersion