The Effect of Folic Acid as Anti Fibrosis in Peritoneum of Rat

Abstract

Wachid Putranto, Bambang Purwanto, Ambar Mudigdo, Brian Washita, Ari Natali Probandari

Introduction: One limitations of Peritoneal Dialysis (PD)’s is peritoneal fibrosis, which is a functional and structural change in the peritoneal membrane induced by peritoneal dialysate fluid containing high sugar levels. This may cause ultrafiltration (UF) failure leading to progressive loss of dialysis efficacy. Expression of vascular endothelial growth factor (VEGF) increases angiogenesis and vascular permeability, followed by increased macromolecular leakage and ultimately contributes to UF failure. Expression of Transforming Growth Factor-β (TGF-β) induces mesothelial thickening and peritoneal fibrosis. Folic acid inhibits progressivity of Chronic Kidney Disease (CKD) by 21% and improve Glomerular Filtration Rate (GFR) by 10% in hypertensive patients. Folic acid can reduce inflammation as cause of endothelial dysfunction that impact to progressive atherosclerosis. The aim of this study was to evaluate the effect folic acid to reduce the expression of TGF-β, VEGF and peritoneal fibrosis in a male rat treated with PD. Methods: This was an experimental study, with post-test only control group design. Twenty-four Sprague dawley rats are divided into four groups: CKD rat group (Group 1), PD liquid 4,25% (Group 2), CKD PD and folic acid 120 µg/day oral (Group 3), and CKD PD & lisinopril 1,5 mg/day oral (Group 4). After 4 weeks, rat sacrificed expression of TGF-β, VEGF and peritoneal fibrosis are conducted by histopathology with masson’s trichrome and immunology with anti-human-TGF-β and anti VEGF. Statistical analys is using Kruskal Willis test. p-value <0.05 was considered statistically significant. Results: Compared with CKD PD group, folic acid group shown decrease of TGF-β expression (p = 0.002), VEGF expression (p = 0.01), and peritoneal fibrosis (p = 0.001). Lisinopril group also showed decrease of TGF-β expression (p = 0.06), VEGF expression (p = 0.09), but not for peritoneal fibrosis. Folic acid decreased TGF-β expression more than lisinopril. The decrease in VEGF expression in the lisinopril group was greater than folic acid group. Conclusion: Folic acid shown lower of TGF-β and VEGF expression and reduced and peritoneum fibrosis better than control or lisinopril and statistically significant. Folic acid is potential as therapy agent to reduce peritoneal fibrosis in PD’s patient