Paricalcitol induces mitochondrial cyto-protective effect during a nephropathy model

LILIANA ALTAMIRANO; ISABEL MERCEDES GARCíA; LUCIANA MAZZEI; LEóN FERDER; WALTER MANUCHA

San Juan

Congreso; 2 reunión Conjunta Sociedades de Biología República Argentina; 2011

Sociedades de Biología de la República Argentina

Background: Growing evidence proposes that vitamin D slows the progression of chronic kidney diseases. Further, activators of vitamin D receptors (VDR) have suppressant effect on the renin-angiotensin system (RAS), as well as anti-inflammatory and anti-fibrotic effects. Aim: This study was performed to evaluate in an obstructive nephropathy model (UUO), possible paricalcitol (Pari) cyto-protective effect at the mitochondrial level. Methods: Ten adult female rats were obstructed surgically and divided into two groups (control or treated). The treatment was done for 15-day duration (30ng/Kg). We evaluated: 1-parathyroid hormone, Ca+2 and P, 2-Fibrosis, apoptosis and mitochondrial morphology, 3-VDR, AT1 receptor, TGF-â and Renox (NOX4) expression and 4)-NADPH oxidase activity. Results: Biochemical, histological and molecular studies shows mitochondrial injury in UUO. Electronic microscopy revealed, electronically luminous nuclear material and the mitochondria were increased in size with dilated crests and spaces in their interior. Also, high AT1 expression and NADPH activity were reverts in paricalcitol-treated animals. Conclusions: These results suggest, in an obstructed nephropathy model, a cyto-protected effect of the activator of Vitamin D receptors, paricalcitol, revealing for the first time a possible protective effect AT1 receptor dependent at the mitochondrial level.