CONICET | Buscador de Institutos y Recursos Humanos

Oxidative stress represents the common denominator of multiple cellular alterations and contributes to tubulointerstitial mechanism damage in neonatal unilateral ureteral obstruction (OUU). From what it is valid to propose alternatives of protection to the injury risk, as statins use that it has demonstrated hypolipemiant effects as well as antioxidant activity and fibrosis decrease. Recently, we demonstrate relation sheep between nitric oxide bioavailability and Hsp70 expression in OUU. Objective: to evaluate possible antioxidant/antiapoptotic effects of rosuvastatin (Ros) during OUU in order to establish nephroprotective mechanisms related to the apoptotic modulation. Methods: Neonatal rats (n=10) with and without unilateral ureteral obstruction (OC and CC) Rosuvastatin treated (10mg/Kg/d) for 14 days, were nephrectomized to evaluate in cortexes: oxidative stress and apoptosis modulator markers. Results: The obstruction showed (OC vs. CC) significative increase in oxidative stress markers as lipid peroxidation (MDA) 90±5 vs 70±4 nmol/mL, NADPH oxidase activity (21682±234 vs. 8200±123 RUF/µg prot/min) and caveolin-1 protein expression (0,98±0,02 vs. 0,55±0,04 ROD). Also, Hsp70 expression decrease (RT-PCR and Western Blot) (0,35±0,04 vs. 0,87±0,05) and less endogenous nitric oxide levels, 67±2 vs. 74±2 nM. Rosuvastatin administration decrease oxidative stress parameters with significative Hsp70 expression increase (0,95±0,05 vs. 0,35±0,04), caveolin-1 expression was decreased (0,50±0,03 vs. 0,98±0,02) and nitric oxide levels was recuperated (100±11 vs. 67±2 nM). Conclusion: Our results demonstrate that Rosuvastatin diminishes oxidative stress and apoptosis during neonatal unilateral ureteral obstruction associated with the decrease in caveolin-1 expression what favors nitric oxide bioavailability. The Hsp70 expression increased, protein of early response to oxidative injury, it would fulfill a citoprotector function againts oxidative stress and apoptosis.