#1144 Role of PPAR-alpha in folic acid-induced tubulointerstitial fibrosis

Abstract

Abstract Background and Aims PPAR-alpha is a nuclear receptor that plays a major role in the regulation of lipid metabolism. Activation of PPAR-alpha has been shown to have beneficial effects in renal diseases. Acute kidney injury (AKI), even if followed by renal recovery, is a risk factor for the future development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Progressive tubulointerstitial fibrosis is the final common pathway for all kidney diseases leading to chronic renal failure. Our main objective was to determine the importance of PPAR-alpha in tubulointerstitial fibrosis in folic acid induced nephropathy. Method Male C57/Bl6 and PPARKO (C57Bl6 background) mice were divided into 4 groups, Control, Folic Acid, Gemfibrozil + Folic Acid and PPARKO + Folic Acid. Animals have been treated with a single dose of Folic Acid (250 mg/kg i.p) and Gemfibrozil (150 mg/kg gavage) euthanized after 28 days for. Renal parameters, histology, real time PCR were performed to investigate renal injury, inflammation, and fibrosis. Results After 28 days of folic acid inducing CKD. PPARKO showed the same levels of injury as folic acid alone treated mice, however PPAR-alpha activation with gemfibrozil decreased urinary volume (Folic Acid: 3.870 ± 0.679 Gemfibrozil: 1,242 ± 0,223), creatinine (Folic Acid: 0,7940 ± 0,0357 Gemfibrozil: 0,5820 ± 0,0288), urea levels (Folic Acid: 79,23 ± 3,20 Gemfibrozil: 46,11 ± 3,874), showed less tubulointerstitial fibrosis (Folic Acid: 0,5837 ± 0,0426), Gemfibrozil: 0,2423 ± 0,0293) and lower urine protein/creatinine ratio (Folic Acid: 5,486 ± 0,588 Gemfibrozil: 2,536 ± 0,127). Conclusion PPAR-alpha deletion did not show protection in chronic phase, in the other hand PPAR-alpha activation with gemfibrozil showed to be effective against tubulointerstitial fibrosis.