THE EFFECT OF SANDOSTATIN IN NEPHROTIC SYNDROME WITH ADRIAMYCIN.
Project no. 16 · Status: Kapanmış · 2016
Summary
Introduction: Nephrotic syndrome is the result of deletion of the podocyte leg protrusions and destruction of the actin skeleton. Deletion of podocyte actin cell skeleton and foot protrusions may result in significant shape changes in podocytes, resulting in severe proteinuria. Therefore, factors leading to phenotypic changes in mature podocytes bring new pathogenic mechanisms to the agenda. Molecular, anatomical and functional properties of podocytes are investigated and directed to the diagnosis and treatment. Since the discovery of the role of cytokine TGF-beta, the main mediator of glomerular and tubulointerstitial pathobiology in recent years, TGF-beta signaling studies in the kidney have focused on the molecular biology of fibrogenesis. In the past decades, several immunomodulating agents have been used to treat glomerular diseases and to reduce proteinuria. In the light of this information, we aimed to investigate the effects of octreotide on proteinuria and inflammation in adriamycin- induced nephrotic syndrome model. Method: In our study, we used Human Podocyte Primary Cell Culture - T75 Plated Cells, Celprogen cell line. The purchased cell line was amplified at 37?C and then divided into 25mL flasks. Then it was transferred to 12 wellplates. 1X106 cells were placed in each well. RPMI 1640 medium was used for cell proliferation. The medium was treated with 10% FBS and IFN-için for cell proliferation and Penicillin / Streptomycin to prevent secondary bacterial growth. FBS and IFN were kept at minimum levels during drug incubations. Standard methods were used for cell line amplification and DMSO, PBS and Trypsin were used for this. Firstly, toxicity caused by increasing doses of adriamycin was investigated. After incubation with adriamycin and octreotide (0.8.24.48.96 hours), TGF-beta was determined by ELISA method in cell lysates. Results: In the nephrotic syndrome model induced by adriamycin, podocyte damage was evaluated with collagen 4 level. Subsequently, proteinuria ratios after octreotide were measured in the cells which were modeled as nephrotic syndrome. Finally, after octreotide, TGF-B levels were measured in the same model. A significant decrease in proteinuria was observed with octreotide at 24th hour and TGF-B levels were decreased at 24th and 48th hours. Conclusion: Proteinuria is a characteristic finding in glomerular diseases. In addition, therapeutic interventions that reduce proteinuria improve renal prognosis. Scientific evidence has shown that podocytes are key modulators for glomerular damage and proteinuria. In our study, in the nephrotic syndrome model induced by adriamycin, antiinflammatory and antiproteinuric findings with octreoid were observed. Key words: Nephrotic sydrome, podocyte, adriamycin, octreotide, TGF-beta.