COX‐2 inhibition exacerbates SOD1 dowregulation and the progression of renal oxidative stress in response to UUO

Abstract

Renal damage and oxidative stress resulting from unilateral ureteral obstruction (UUO) may be aggravated by reactive oxygen species (ROS). Deleterious effects of ROS are attenuated by antioxidant enzymes. We investigated the role of COX‐2 in the progression of renal oxidative stress induced by UUO in mice.Mice were subjected to UUO and treated with the selective COX‐2 inhibitor parecoxib for 7 days. Using immunoblot analysis, we examined the regulation of antioxidant enzymes, catalase, superoxid dismutase 1 and 2 (SOD1 and −2) in renal cortex and inner medulla. Immunohistochemistry was performed with oxidative stress markers.COX‐1 and −2 protein were increased in response to UUO. SOD1 and −2 protein were increased in IM in parecoxib treated sham operated mice. Parecoxib treated UUO mice had more reduced SOD1 protein level in IM and cortex than untreated UUO mice, whereas SOD2 and cortical catalase protein levels were unchanged.COX‐2 inhibition increased the renal SOD1 and −2, consistent with a stress response to increased ROS production. UUO reduced SOD1 and catalase, and inhibited increased SOD1 and −2 seen with COX‐2 inhibition.In conclusion, suppression of renal antioxidant enzymes by UUO contributes to the progression of renal oxidative stress, a process exacerbated by COX‐2 inhibition.