Inhibition of COX 1 and 2 prior to Renal Ischemia/Reperfusion Injury Decreases the Development of Fibrosis

Autor: Felipe Caetano Beraldo, Giselle Martins Gonçalves, Niels Olsen Saraiva Câmara, Alvaro Pacheco-Silva, Hélady Sanders Pinheiro, Patricia Semedo, Oscar Fernando, Carla Q. Feitoza, Marilda Mazzali, Vicente de Paula Antunes Teixeira, Pavão dos Santos, Marlene Antonio dos Reis, Marcos Antonio Cenedeze
Rok vydání: 2008
Předmět:
Male
Bone Morphogenetic Protein 7
Indomethacin
Interleukin-1beta
Gene Expression
Kidney
Kidney Function Tests
Mice
chemistry.chemical_compound
Transforming Growth Factor beta
Fibrosis
Osteopontin
Chemokine CCL2
Research Articles
Genetics (clinical)
biology
Reverse Transcriptase Polymerase Chain Reaction
Immunohistochemistry
Interleukin-10
medicine.anatomical_structure
Reperfusion Injury
Molecular Medicine
medicine.medical_specialty
Collagen Type I
Proinflammatory cytokine
Internal medicine
Genetics
medicine
Animals
Vimentin
Cyclooxygenase Inhibitors
Molecular Biology
Sirius Red
Tumor Necrosis Factor-alpha
business.industry
Connective Tissue Growth Factor
Kidney metabolism
medicine.disease
CTGF
Endocrinology
chemistry
Cyclooxygenase 2
Immunology
Cyclooxygenase 1
biology.protein
business
Reperfusion injury
Heme Oxygenase-1
Zdroj: Molecular Medicine. 14:724-730
ISSN: 1528-3658
1076-1551
Popis: Ischemia and reperfusion injury (IRI) contributes to the development of chronic interstitial fibrosis/tubular atrophy in renal allograft patients. Cyclooxygenase (COX) 1 and 2 actively participate in acute ischemic injury by activating endothelial cells and inducing oxidative stress. Furthermore, blockade of COX 1 and 2 has been associated with organ improvement after ischemic damage. The aim of this study was to evaluate the role of COX 1 and 2 in the development of fibrosis by performing a COX 1 and 2 blockade immediately before IRI. We subjected C57Bl/6 male mice to 60 min of unilateral renal pedicle occlusion. Prior to surgery mice were either treated with indomethacin (IMT) at days -1 and 0 or were untreated. Blood and kidney samples were collected 6 wks after IRI. Kidney samples were analyzed by real-time reverse transcription-polymerase chain reaction for expression of transforming growth factor beta (TGF-beta), monocyte chemoattractant protein 1 (MCP-1), osteopontin (OPN), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1 beta, IL-10, heme oxygenase 1 (HO-1), vimentin, connective-tissue growth factor (CTGF), collagen I, and bone morphogenic protein 7 (BMP-7). To assess tissue fibrosis we performed morphometric analyses and Sirius red staining. We also performed immunohistochemical analysis of anti-actin smooth muscle. Renal function did not significantly differ between groups. Animals pretreated with IMT showed significantly less interstitial fibrosis than nontreated animals. Gene transcript analyses showed decreased expression of TGF-beta, MCP-1, TNF-alpha, IL-1-beta, vimentin, collagen I, CTGF, and IL-10 mRNA (all P0.05). Moreover, HO-1 mRNA was increased in animals pretreated with IMT (P0.05). Conversely, IMT treatment decreased osteopontin expression and enhanced BMP-7 expression, although these levels did not reach statistical significance when compared with control expression levels. The blockade of COX 1 and 2 resulted in less tissue fibrosis, which was associated with a decrease in proinflammatory cytokines and enhancement of the protective cellular response.
Databáze: OpenAIRE
Externí odkaz: