Effect of atorvastatin and erythropoietin on renal fibrosis induced by partial unilateral ureteral obstruction in rats

Abstract

ObjectiveThis work aims at investigating the effects of atorvastatin and erythropoietin (EPO) on tubulointerstitial fibrosis induced by partial unilateral ureteral obstruction (PUUO) in rats.BackgroundRenal fibrosis is the final manifestation of chronic kidney disease. It is one of the biggest problems in nephrology, indicating that patients inevitably reach end-stage renal disease. Atorvastatin has anti-inflammatory, antiproliferative, and immunomodulatory potential. EPO has been demonstrated to play an important cytoprotective role.MethodsFifty adult albino rats were divided into five equal groups: group 1 received saline intraperitoneally and methylcellulose orally for 14 days and served as the negative control; group 2 (sham-operated group) rats underwent the same surgical procedures as group 3 without ureteral obstruction; group 3 rats underwent PUUO without any medication; group 4 rats underwent PUUO and received atorvastatin at a dose of 50 mg/kg orally; group 5 rats underwent PUUO and received EPO at a dose of 3.000 IU/kg daily intraperitoneally. After 14 days, systolic blood pressure was measured. Blood and urine samples were also collected for measurement of serum transforming growth factor-β1, tumor necrosis factor-͍, urea and creatinine, and urinary protein and albumin levels. Renal tissue samples were collected for determination of malondialdehyde and ͍-smooth muscle actin levels, as well as for histopathological and immuonohistochemical examination.ResultsOur results showed that systolic blood pressure; serum levels of transforming growth factor-β1, tumor necrosis factor-α, and malondialdehyde; and biochemical parameters were significantly elevated. Histopathological examination of kidney tissue revealed marked degenerative changes and increased expression of α-smooth muscle actin in group 3 compared with groups 1 and 2. In contrast, biochemical, histological, and immuonohistochemical features in groups 4 and 5 showed significant improvement compared with group 3.ConclusionIt is concluded that both atorvastatin and EPO have renoprotective effects against renal fibrosis, shown by improvement in kidney functions and using fibrosis markers.