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Analysis of the effect of tamoxifen and BMP-7 in experimental model of peritoneal fibrosis in rats with chronic kidney disease

Grant number: 11/05614-1
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): August 01, 2011
Effective date (End): May 31, 2013
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Irene de Lourdes Noronha
Grantee:Filipe Miranda de Oliveira Silva
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Peritoneal dialysis is an extremely important therapeutic option for patients with chronic kidney disease (CKD) in the terminal stage. However, in the long term, morphofunctional changes resulting from bioincompatibilidade of dialysis solutions and establish an infection peritoneal inflammation and fibrosis of the peritoneal membrane, leading to loss of dialysis efficacy of this method. It's worth noting that the state of uremic patients intensifies the inflammation of the peritoneal membrane, thus being an aggravating factor. Therapeutic strategies that can prevent injury and/or block the fibrogenic process of the peritoneal membrane of patients with CKD on dialysis are extremely important. In this context, this study aims to establish a model of fibrosing peritonitis associated with CKD with uremia, mimicking that found in clinical practice, and analyze the effect of two antifibrotic molecules in this model, tamoxifen and BMP-7 in order to propose new strategies for blocking the peritoneal fibrosis. The CKD will be with uremia induced in rats by administration of adenine-rich diet during the period of 30 days, and in the last 15 days the animals receive intraperitoneal injections of chlorhexidine gluconate for the induction of peritonitis. Treatments with tamoxifen and BMP-7 will be started at the same time the administration of chlorhexidine gluconate. During the monitoring period (30 days) will be checked: animal weight, blood pressure and serum urea and creatinine. At the end of monitoring period, the animals are sacrificed and the peritoneum is analyzed by histology (hematoxylin and eosin and Masson Trichrome), to assess thickening peritoneal subserosal fibrosis; immunohistochemistry for macrophages, T lymphocytes and myofibroblasts (±-smooth muscle actin) and to correlate these cellular components to the model and the proposed treatments; and real-time PCR to correlate the expression of proinflammatory cytokines (MCP-1, IL-1ß, TNF-±, INF-³ and IL-6) and fibrogenic factors (VEGF, TGF-ß1, collagen I, collagen III and fibronectin) with the model and the proposed treatments. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SILVA, FILIPE M. O.; COSTALONGA, ELERSON C.; SILVA, CLEONICE; CARREIRA, ANA C. O.; GOMES, SAMIRAH A.; SOGAYAR, MARI C.; FANELLI, CAMILLA; NORONHA, IRENE L.. Tamoxifen and bone morphogenic protein-7 modulate fibrosis and inflammation in the peritoneal fibrosis model developed in uremic rats. Molecular Medicine, v. 25, n. 1, . (11/05614-1, 13/16269-9)

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