OBJECTIVE AND DESIGN: This work explored the role of inhibition of cyclooxygenases (COXs) in modulating the inflammatory response triggered by acute kidney injury. MATERIAL: C57Bl/6 mice were used. TREATMENT: Animals were treated or not with indomethacin (IMT) prior to injury (days -1 and 0). METHODS: 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-1beta, heme oxygenase (HO)-1, and prostaglandin E synthase (PGES) messenger RNA (mRNA) were studied. Cytokines were quantified in serum. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE AND DESIGN: This work explored the role of inhibition of cyclooxygenases (COXs) in modulating the inflammatory response triggered by acute kidney injury. MATERIAL: C57Bl/6 mice were used. TREATMENT: Animals were treated or not with indomethacin (IMT) prior to injury (days -1 and 0). METHODS: Animals were subjected to 45 min of renal pedicle occlusion and sacrificed at 24 h after reperfusion. Serum creatinine and blood ureanitrogen, 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-1beta, heme oxygenase (HO)-1, and prostaglandin E synthase (PGES) messenger RNA (mRNA) were studied. Cytokines were quantified in serum. RESULTS: 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. CONCLUSIONS: 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.
Authors: K Yamamoto; T Arakawa; Y Taketani; Y Takahashi; Y Hayashi; N Ueda; S Yamamoto; M Kumegawa Journal: Adv Exp Med Biol Date: 1997 Impact factor: 2.622
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Authors: G M Gonçalves; M A Cenedeze; C Q Feitoza; P M H Wang; A P F Bertocchi; M J Damião; H S Pinheiro; V P Antunes Teixeira; M A dos Reis; A Pacheco-Silva; N O S Câmara Journal: Kidney Int Date: 2006-09-27 Impact factor: 10.612
Authors: Zhiguo Chen; Lori K Phillips; Elizabeth Gould; Jay Campisi; Star W Lee; Brandi K Ormerod; Monika Zwierzchoniewska; Olivia M Martinez; Theo D Palmer Journal: PLoS One Date: 2011-03-30 Impact factor: 3.240