Differential toxicity of arsenic on renal oxidative damage and urinary metabolic profiles in normal and diabetic mice
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Diabetes is a common metabolic disease, which might influence susceptibility of the kidney to arsenic toxicity. However, relative report is limited. In this study, we compared the influence of inorganic arsenic (iAs) on renal oxidative damage and urinary metabolic profiles of normal and diabetic mice. Results showed that iAs exposure increased renal lipid peroxidation in diabetic mice and oxidative DNA damage in normal mice, meaning different effects of iAs exposure on normal and diabetic individuals. Nuclear magnetic resonance (NMR)-based metabolome analyses found that diabetes significantly changed urinary metabolic profiles of mice. Oxidative stress-related metabolites, such as arginine, glutamine, methionine, and β-hydroxybutyrate, were found to be changed in diabetic mice. The iAs exposure altered amino acid metabolism, lipid metabolism, carbohydrate metabolism, and energy metabolism in normal and diabetic mice, but had higher influence on metabolic profiles of diabetic mice than normal mice, especially for oxidative stress-related metabolites and metabolisms. Above results indicate that diabetes increased susceptibility to iAs exposure. This study provides basic information on differential toxicity of iAs on renal toxicity and urinary metabolic profiles in normal and diabetic mice and suggests that diabetic individuals should be considered as susceptible population in toxicity assessment of arsenic.
KeywordsArsenic Diabetes Oxidative damage Metabolic profiles Kidney Mouse
This work was supported by Natural Science Foundation of Jiangsu Province (BK20131270), Foundation of State Key Laboratory of Pollution Control and Resource Reuse, and Fundamental Research Funds for the Central Universities of Nanjing University.
Compliance with ethical standards
Compliance with the NIH Guide for the Care and Use of Laboratory Animals. And the protocol was approved by the Committee on the Ethics of Animal Experiments of the Nanjing Military General Hospital.
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