APOCYNIN PREVENTS BLOOD PRESSURE RISING AND IMPROVES KIDNEY FUNCTION IN RATS WITH 5/6 NEPHRECTOMY

Objective: High blood pressure and proteinuria play major roles in chronic kidney disease (CKD), a high-mortality condition that affects millions of people. Reactive oxygen species (ROS) produced by NADPH oxidases are implicated in many pathophysiological processes including hypertension and CKD. Apocynin (APO) shows the anti-oxidative activity by inhibiting the assembly of NADPH oxidase and overproduction of ROS. The aim of this study was to investigate the effects of apocynin on oxidative stress, blood pressure and kidney function in normotensive rats with CKD induced by 5/6 nephrectomy through ligation of renal poles (Nx-L). Design and method: Male Wistar rats were divided into three groups. One group was control (sham surgery) and two other groups underwent two-step surgical procedure of 5/6 nephrectomy induced by ligation of renal poles. Unlike conventional Nx which leads to high mortality due to hemorrhage in or after surgery, here we induced Nx by ligation of the upper and lower poles (leads to necrosis of these poles) of left kidney after removal the right kidney one week later. After 4 weeks from this procedure, control and model group (Nx-L) received vehicle, while Nx-L+APO received apocynin 20 mg/kg/day (i.p.) for 4-week-period. Mean blood pressure (MAP), proteinuria, and oxidative stress marker (thiobarbituric acid reactive species-TBARS) in plasma and urine were measured. Results: In model group we observed significantly increased MAP (121,13±2,01vs.94,88±4,13mmHg, p<0.001), plasma creatinine (55,4±1,3vs. 41,3±2,3μmol/l, p<0.001), and proteinuria (0,036±0,006vs.0,017±0,001mg/min/kg, p<0.01) levels compared to those in control. Furthermore, significant increase of plasma TBARS level (5,47±0,77vs.2,75±0,52nmol/ml, p<0.01) and urine TBARS excretion (1,10±0,06vs.0,86±0,04nmol/min/kg, p<0.01) were detected in model compared to control. Interestingly, APO treatment significantly reduced blood pressure to the level of control (83,88±5,14vs.94,88±4,13mmHg). APO significantly reduced urine protein loss (0,024±0,002vs.0,036±0,006mg/min/kg, p<0.05) and plasma creatinine level (49,9±1,5vs.55,4±1,3μmol/l, p<0.05) as well as reduced plasma lipid peroxidation (2,19±0,26vs.5,47±0,77nmol/ml, p<0.001) in comparison to model group. Conclusions: Our results show that APO treatment prevents blood pressure rising and ameliorates kidney function in rats with 5/6 nephrectomy trough improvement of systemic oxidative status. Therefore, NADPH oxidase presents a potential therapeutic target in this form of kidney disease.