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Title: Modulation of inflammatory response by selective inhibition of cyclooxygenase-1 and cyclooxygenase-2 in acute kidney injury
Authors: Feitoza, Carla Q. [UNIFESP]
Semedo, Patricia [UNIFESP]
Goncalves, Giselle M. [UNIFESP]
Cenedeze, Marcos A. [UNIFESP]
Pinheiro, Helady S.
Pavao dos Santos, Oscar Fernando [UNIFESP]
Landgraf, Richardt Gama [UNIFESP]
Pacheco-Silva, Alvaro [UNIFESP]
Saraiva Camara, Niels Olsen [UNIFESP]
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Univ Fed Juiz de Fora
Hosp Israelita Albert Einstein
Keywords: Cyclooxygenase
Renal ischemia and reperfusion injury
Heme oxygenase 1
Issue Date: 1-Mar-2010
Publisher: Birkhauser Verlag Ag
Citation: Inflammation Research. Basel: Birkhauser Verlag Ag, v. 59, n. 3, p. 167-175, 2010.
Abstract: 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.
ISSN: 1023-3830
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Appears in Collections:Em verificação - Geral

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