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Effects of apocynin and losartan treatment on renal oxidative stress in a rat model of calcium oxalate nephrolithiasis

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Abstract

Background

Tissue culture studies found that renal epithelial cells suffer oxidative injury on exposure to high levels of oxalate (Ox) and calcium oxalate (CaOx) crystals; nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a major source of reactive oxygen species (ROS) production in kidney, has been shown to be involved in this event. The present study aimed to investigate whether this in vitro feature of NADPH oxidase could be confirmed in vivo.

Methods

Animal model of nephrolithiasis was established in adult male Sprague-Dawley rats by administration of 0.8% ethylene glycol (EG) in drinking water for 4 weeks. Simultaneous treatment with apocynin (0.2 g kg−1 day−1) or losartan (30 mg kg−1 day−1) by intragastric administration was performed in rats. At the end of the study, urinary 8-IP, a product of lipid peroxidation, and enzymatic activity of superoxide dismutase (SOD) in kidney homogenates were assessed as markers for state of renal oxidative stress (OS). Expression of NADPH oxidase subunit p47phox in kidney was localized and evaluated by immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blotting. The concentration of angiotensin II in kidney homogenates was determined using radioimmunoassay method.

Results

Compared with control, OS developed significantly in rats received EG, with increased expression of p47phox messenger RNA (mRNA) and protein in kidneys. Renal angiotensin II also increased significantly. Treatment with apocynin or losartan significantly reduced excretion of urinary 8-IP, restored SOD activity, with decrease in expression of p47phox in kidney, but levels of those OS markers in apocynin- or losartan-treated rats were still higher than in normal controls.

Conclusions

These results suggest that renal Ang II and its stimulation of NADPH oxidase may partially account for the development of OS in kidney in this rat model of CaOx nephrolithiasis.

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Acknowledgements

This study was supported by the Major Program of Guangxi Zhuang Autonomous Region Bureau of Health (No. 200729), the Guangxi Science and Technology Development Program (No. 0816004-4), and the Postgraduate Innovation Program (No. 309083).

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  1. Department of Urology, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China

    Cheng-yang Li, Yao-liang Deng & Bing-hua Sun

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  1. Cheng-yang Li
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Correspondence to Yao-liang Deng.

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Li, Cy., Deng, Yl. & Sun, Bh. Effects of apocynin and losartan treatment on renal oxidative stress in a rat model of calcium oxalate nephrolithiasis. Int Urol Nephrol 41, 823–833 (2009). https://doi.org/10.1007/s11255-009-9534-0

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