Fibrosis and Apoptosis Gene Pattern in Neonatal Obstrutive Nephrology: Rosuvastatin Modulation

MAZZEI LUCIANA; GARCÍA MERCEDES; BENARDON MARIA EUGENIA; CACCIAMANI VALERIA; GARRAMUÑO VALLÉS PATRICIA; MANUCHA WALTER

La Punta,San Luis

Congreso; XXVII Reunión Científica Anual Sociedad de Biología de Cuyo; 2009

Sociedad de Biología de Cuyo

Oxidative stress represents the common denominator of multiple cellular alterations and contributes to tubulointerstitial mechanism damage in neonatal unilateral ureteral obstruction (UUO). Proposed alternatives of protection to renal injury include statin, due to its effects decreasing oxidative stress and tubulointerstitial fibrosis. Recently, we have demonstrated an association between nitric oxide (NO) bioavailability and Hsp70 expression in UUO. The goal was to evaluate possible antioxidant/antiapoptotic effects of rosuvastatin (Ros) during UUO in order to establish its nephroprotective effects. Neonatal rats (n=5) with and without UUO (OC and CC) and Ros treated rats (10mg/Kg/d) for 14 days, were nephrectomized to evaluate in cortexes oxidative stress and heat shock response. After 14 days of obstruction, oxidative stress markers as lipid peroxidation (MDA) (90±5 vs 70±4 nmol/mL) and NADPH oxidase activity (21682±234 vs. 8200±123 RUF/µg prot/min) increased, whereas hsf1 and Hsp70 expression (0.35±0.04 vs. 0.87±0.05) and lower endogenous nitric oxide levels (67±2 vs. 74±2 nM) decreased. Conversely,Oxidative stress represents the common denominator of multiple cellular alterations and contributes to tubulointerstitial mechanism damage in neonatal unilateral ureteral obstruction (UUO). Proposed alternatives of protection to renal injury include statin, due to its effects decreasing oxidative stress and tubulointerstitial fibrosis. Recently, we have demonstrated an association between nitric oxide (NO) bioavailability and Hsp70 expression in UUO. The goal was to evaluate possible antioxidant/antiapoptotic effects of rosuvastatin (Ros) during UUO in order to establish its nephroprotective effects. Neonatal rats (n=5) with and without UUO (OC and CC) and Ros treated rats (10mg/Kg/d) for 14 days, were nephrectomized to evaluate in cortexes oxidative stress and heat shock response. After 14 days of obstruction, oxidative stress markers as lipid peroxidation (MDA) (90±5 vs 70±4 nmol/mL) and NADPH oxidase activity (21682±234 vs. 8200±123 RUF/µg prot/min) increased, whereas hsf1 and Hsp70 expression (0.35±0.04 vs. 0.87±0.05) and lower endogenous nitric oxide levels (67±2 vs. 74±2 nM) decreased. Conversely, Rosuvastatin administration increased hsf1 and Hsp70 expression linked to increase in NO levels with absence of apoptotic response and decreased oxidative stress. These findings suggest that Rosuvastatin exerts citoprotective effects against oxidative stress through NO restoration and upregulation of hsf1 and Hsp70 in neonatal unilateral ureteral obstruction Rosuvastatin administration increased hsf1 and Hsp70 expression linked to increase in NO levels with absence of apoptotic response and decreased oxidative stress. These findings suggest that Rosuvastatin exerts citoprotective effects against oxidative stress through NO restoration and upregulation of hsf1 and Hsp70 in neonatal unilateral ureteral obstruction