COX‐2 induction is ROS dependent in rats during 3 days unilateral ureteral obstruction

Abstract

Oxidative stress may contribute to cellular dysfunction of the kidney with unilateral ureteral obstruction (UUO). Previously we have shown induction of cyclooxygenase type 2 (COX‐2) in renal medullary interstitial cells (RMIC) during UUO. This study investigated the role of oxidative stress or ROS in the induction of COX‐2 during UUO.Rats were subjected to 3dUUO and treated with inhibitors of the ROS production (NADPH‐oxidase inhibitor diphenylene iodonium (DPI) and the complex‐1 inhibitor rotenone (ROT)). Clearance experiments were performed. The kidneys were removed and prepared for immunoblotting or immunohistochemistry (IHC) analyses.Bodyweight (BW) was unchanged in 3dUUO rats subjected to DPI whereas ROT decreases BW. Hematoxylin and eosin (HE) staining of the kidney showed lower degree of dilatation due to DPI or ROT treatment in 3dUUO rats. COX‐2 and the oxidative stress marker heme‐oxygenase type 1 (HO‐1) was both increased in inner medulla in response to 3dUUO. This was attenuated by DPI or ROT administration. IHC confirmed these findings. COX‐1 was not changed in 3dUUO rats subjected to DPI or ROT. Plasma urea was not affected by DPI or ROT treatment in response to 3dUUO. HE staining of heart, liver, and brain did not reveal any obvious changes due to administration of DPI or ROT.These results suggest that oxidative stress contribute to the regulation of COX‐2 in inner medulla in rats subjected to 3 days UUO.