Role of Nrf2 in protection against oxidative stress during obstructive nephropaty.

MARTÍN E RINALDI TOSI; VICTORIA BOCANEGRA; VALERIA CACCIAMANI; MARÍA EUGENIA BENARDÓN; ANDREA GIL LORENZO; WALTER MANUCHA; PATRICIA G. VALLES

Centro de Congresos y Exposiciones de Mendoza

Congreso; XXVIII Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2010

Sociedad de Biología de Cuyo

Perturbation of renal tubular antioxidants and overproduction of ROS may amplify the proinflammatory state of renal obstruction, culminating in tubular loss. We analyzed the signal transduction of Nrf2 transcription factor on oxidative stress modulation in UUO. Rats were subjected to UUO or sham operation and kidneys harvested at 5, 7, 10 and 14 days after obstruction. Nrf2 activity and its downstream target gene products were assessed. After 10 and 14 days of obstruction, enhanced lipid peroxidation through higher TBARS levels and increased oxidative stress, resulted in reduced total antioxidant activity and enhanced NADPH oxidase activity were demonstrated. This was accompanied by progressive reduction of nuclear Nrf2 and its target gene products GSTA2 and NQO1, whereas the Nrf2 repressor Keap1 was upregulated. By contrast, on early obstruction for 7 days; lack of increased oxidative markers associated with a rapid nuclear accumulation of Nrf2, Keap1 downregulation and mRNA induction of the identified Nrf2-dependent genes, NQO1 and GSTA2, were shown. We suggest that the cytoprotection in early obstruction depends of induced activation of Nrf2 upregulating its downstream gene products response. Impaired ability to mount the biological response to the prevailing oxidative stress leading to renal injury was shown in prolonged obstruction.