Simvastatin attenuates renal inflammation, tubular transdifferentiation and interstitial fibrosis in rats with unilateral ureteral obstruction

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2005-08, Vol.20 (8), p.1582-1591
• Main Authors: Mauro Vieira, José, Mantovani, Eduardo, Tavares Rodrigues, Leonardo, Dellê, Humberto, Noronha, Irene Lourdes, Fujihara, Clarice Kazue, Zatz, Roberto
• Format: Article
• Language: English
• Subjects: Actins - genetics; Actins - metabolism; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Cell Differentiation - drug effects; Chemokine CCL2 - metabolism; Collagen - genetics; Collagen - metabolism; Emergency and intensive care: renal failure. Dialysis management; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - metabolism; Fibronectins - genetics; Fibronectins - metabolism; Fibrosis - prevention & control; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; inflammation; Intensive care medicine; interstitial fibrosis; Kidney Tubules - drug effects; Kidney Tubules - pathology; Male; MCP-1; Medical sciences; Nephritis, Interstitial - metabolism; Nephritis, Interstitial - pathology; Nephritis, Interstitial - prevention & control; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Proliferating Cell Nuclear Antigen - metabolism; Rats; Rats, Wistar; Renal failure; simvastatin; Simvastatin - therapeutic use; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; transdifferentiation; Transforming Growth Factor beta - metabolism; unilateral ureteral obstruction; Ureteral Obstruction - drug therapy; Ureteral Obstruction - metabolism
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfh859

Background. The pleiotropic actions of statins have been largely explored. These drugs have been tested in several models of progressive renal disease, most of them accompanied by hypertension. We sought to investigate more closely the effects of simvastatin on renal interstitial fibrosis due to unilateral ureteral obstruction (UUO). Methods. Munich-Wistar rats were submitted to UUO and studied after 14 days. Animals were divided into two groups: vehicle (VH) or simvastatin (SIMV) 2 mg/kg b.i.d. by gavage. At sacrifice kidneys were harvested for morphology, mRNA and protein analysis. RT–PCR was done to assess expression of collagen I and III, fibronectin, MCP-1, TGF-β1 and bFGF. Protein expression was assessed by western blot (TGF-β) and immunostaining (macrophage, lymphocyte, PCNA, vimentin and α-smooth muscle actin). Contralateral kidneys (CL) were used as controls. Results. SIMV-treated animals had less severe renal inflammation. MCP-1 was markedly expressed in obstructed kidneys and diminished with SIMV (48.9± 2.5 vs 64.3±3.1 OD in VH, P