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Metabonomics revealed xanthine oxidase-induced oxidative stress and inflammation in the pathogenesis of diabetic nephropathy

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Abstract

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM), which is a major public health problem in the world. To reveal the metabolic changes associated with DN, we analyzed the serum, urine, and renal extracts obtained from control and streptozotocin (STZ)-induced DN rats by 1H NMR-based metabonomics and multivariate data analysis. A significant difference between control and DN rats was revealed in metabolic profiles, and we identified several important DN-related metabolites including increased levels of allantoin and uric acid (UA) in the DN rats, suggesting that disturbed purine metabolism may be involved in the DN. Combined with conventional histological and biological methods, we further demonstrated that xanthine oxidase (XO), a key enzyme for purine catabolism, was abnormally activated in the kidney of diabetic rats by hyperglycemia. The highly activated XO increased the level of intracellular ROS, which caused renal injury by direct oxidative damage to renal cells, and indirect inducing inflammatory responses via activating NF-κB signaling pathway. Our study highlighted that metabonomics is a promising tool to reveal the metabolic changes and the underlying mechanism involved in the pathogenesis of DN.

In this study, we performed 1H NMR-based metabonomic to analyze the serum, urine, and renal extracts in a rat model of diabetic nephropathy (DN), and identified the disturbed purine metabolism and its underlying xanthine oxidase induced oxidative stress and inflammation was involved in the pathogenesis of DN

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Acknowledgments

The authors would like to thank Dr. Pengchi Deng in Analytical & Testing Center of Sichuan University for NMR analysis. This work was supported by grants from National Natural Science Foundation of China (31200754, 30930088) and China Postdoctoral Science Foundation (2012 M511931).

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Authors and Affiliations

  1. Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, No. 1 Keyuan 4th Road, Gaopeng Ave, Chengdu, 610041, China

    Jingping Liu, Chengshi Wang, Yanrong Lu & Jingqiu Cheng

  2. Division of Nephrology, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, China

    Fang Liu

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  1. Jingping Liu
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  2. Chengshi Wang
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  3. Fang Liu
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Correspondence to Yanrong Lu or Jingqiu Cheng.

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Liu, J., Wang, C., Liu, F. et al. Metabonomics revealed xanthine oxidase-induced oxidative stress and inflammation in the pathogenesis of diabetic nephropathy. Anal Bioanal Chem 407, 2569–2579 (2015). https://doi.org/10.1007/s00216-015-8481-0

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  • DOI: https://doi.org/10.1007/s00216-015-8481-0

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