Oxidative stress contributes to orthopedic trauma-induced acute kidney injury in obese rats

Abstract

After trauma, obese patients have an increased risk of developing acute kidney injury (AKI). We have demonstrated that obese Zucker (OZ) rats, but not lean Zucker (LZ) rats, develop AKI 24 h after orthopedic trauma. ROS have been implicated in the pathophysiology of AKI in models of critical illness. However, the contribution of ROS to trauma-induced AKI in the setting of obesity has not been determined. We hypothesized that AKI in OZ rats after trauma is mediated by increased oxidative stress. Male LZ and OZ rats were divided into control and trauma groups, with a subset receiving treatment after trauma with the antioxidant apocynin (50 mg/kg ip, 2 mM in drinking water). The day after trauma, glomerular filtration rate, plasma creatinine, urine kidney injury molecule-1, and albumin excretion as well as renal oxidant and antioxidant activity were measured. After trauma, compared with LZ rats, OZ rats exhibited a significant decrease in glomerular filtration rate along with significant increases in plasma creatinine and urine kidney injury molecule-1 and albumin excretion. Additionally, oxidative stress was significantly increased in OZ rats, as evidenced by increased renal NADPH oxidase activity and urine lipid peroxidation products (thiobarbituric acid-reactive substances), and OZ rats also had suppressed renal superoxide dismutase activity. Apocynin treatment significantly decreased oxidative stress and AKI in OZ rats but had minimal effects in LZ rats. These results suggest that ROS play an important role in AKI in OZ rats after traumatic injury and that ROS may be a potential future therapeutic target in the obese after trauma.

Keywords: acute kidney injury; inflammation; obesity; reactive oxygen species; trauma.

Fig. 1.

Glomerular filtration rate (GFR; A) and plasma creatinine (B) in lean Zucker (LZ) and obese Zucker (OZ) rats in control and trauma groups with or without apocynin treatment. n = 6–8 rats/group. *P < 0.05 vs. control LZ or OZ rats, respectively; +P < 0.05 vs. LZ rats with trauma; #P < 0.05 vs. OZ rats with trauma.

Fig. 2.

Twenty-four-hour urine kidney injury molecule (KIM)-1 (A) and urine albumin-to-creatinine ratio (B) in LZ and OZ rats in control and trauma groups with or without apocynin treatment. n = 6–8 rats/group. *P < 0.05 vs. control LZ or OZ rats, respectively; +P < 0.05 vs. LZ rats with trauma; #P < 0.05 vs. OZ rats with trauma.

Fig. 3.

NADPH oxidase activity (A) and total SOD activity (B) in homogenized renal tissue as well as urine thiobarbituric acid-reactive substances (TBARS; C) in LZ and OZ rats in control and trauma groups with or without apocynin treatment. n = 6–8 rats/group. *P < 0.05 vs. control OZ rats; +P < 0.05 vs. the corresponding LZ group; #P < 0.05 vs. OZ rats with trauma; %P < 0.05 vs. control LZ rats.

Fig. 4.

A and B: plasma TNF-α (A) and IL-10 (B) in LZ and OZ rats in control and trauma groups with or without apocynin treatment. C and D: IL-6 (C) and myeloperoxidase (MPO) activity (D) in homogenized renal tissue of LZ and OZ rats in control and trauma groups with or without apocynin treatment. n = 6–8 rats/group. *P < 0.05 vs. control LZ or OZ rats, respectively; +P < 0.05 vs. LZ rats with trauma; #P < 0.05 vs. OZ rats with trauma.