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

Author(s)

Feitoza, Carla Q. ^[1] ; Semedo, Patricia ^[1] ; Goncalves, Giselle M. ^[1] ; Cenedeze, Marcos A. ^[1] ; Pinheiro, Helady S. ^[2] ; Pavao dos Santos, Oscar Fernando ^[1] ; Landgraf, Richardt Gama ^[3] ; Pacheco-Silva, Alvaro ^{[4, 1]} ; Saraiva Camara, Niels Olsen ^{[1, 5]}

Affiliation

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

^[2] Univ Fed Juiz de Fora, Div Nephrol, Juiz De Fora, MG - Brazil

^[3] Univ Fed Sao Paulo, Dept Biol Sci, Sao Paulo - Brazil

^[4] Hosp Israelita Albert Einstein, Inst Ensino & Pesquisa, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Transplantat Immunobiol Lab, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: Inflammation Research; v. 59, n. 3, p. 167-175, MAR 2010.
• Web of Science Citations: 12

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. (AU)

• FAPESP's process: 06/03982-5 - Molecular aspects involved in leukocytes microbicidal and inflammatory activities in the lung
• Grantee: Sônia Jancar
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 07/07139-3 - The role of heme oxygenase 1 in different renal inflammatory process in experimental animal models
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants