Analysis of the effect of tamoxifen and BMP-7 in an experimental model of peritoneal fibrosis in rats with Chronic Kidney Disease

• Grant number: 13/16269-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2013
• End date: September 30, 2015
• 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

Abstract

Peritoneal dialysis is an extremely important therapeutic option for patients with Chronic Kidney Disease (CKD) stage V. However, long-term morphological changes resulting from bioincompatibility of dialysis solutions, peritoneal infections and the state of uremic patients, induce an inflammatory and fibrotic process of the peritoneal membrane, leading to loss of effectiveness of this dialytic method.In this study, CKD with uremia is induced in male Wistar rats by administering a diet rich in adenine, during the 30 day period, whereas the last 15 days, the animals receive intraperitoneal injections of Chlorhexidine Gluconate (CG) to induce peritonitis. Treatment with tamoxifen and BMP-7 will be started in the same period of administration of GC. During the monitoring period will be checked: weight, blood pressure and serum urea and creatinine. At the end of the monitoring period, the animals will be sacrificed and the peritoneum analyzed by histology (Masson Trichrome), immunohistochemistry for macrophages, T lymphocytes, myofibroblasts (+ smooth muscle actin) and PCNA, and real-time PCR for the expression of pro-inflammatory cytokines (IL-1ß, TNF-±, IFN-³ and IL-6) and fibrogenic factors (VEGF, TGF-ß1, collagen I, collagen III, fibronectin and FSP-1). It will also be performed real-time PCR and Western Blot for the expression of Smad 2, 3, 5 and 7. In addition, Western Blot will be made for the same Smads, however, in its phosphorylated form. Finally, an in vitro study using immortalized mesothelial cells will be carried out to elucidate the mechanisms involved in fibrogenesis in the peritoneum. (AU)

Scientific publications

(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, AUG 28 2019. (11/05614-1, 13/16269-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Filipe Miranda de Oliveira. Analysis of the effect of tamoxifen and BMP-7 in an experimental model of peritoneal fibrosis in rats with chronic kidney disease. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.