Metabolomics analysis of the effects of quercetin on renal toxicity induced by cadmium exposure in rats
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Metabolomics analysis of the effects of quercetin on renal toxicity induced by cadmium exposure in rats Tong Guan . Youwei Xin . Kai Zheng . Ruijuan Wang . Xia Zhang . Siqi Jia . Siqi Li . Can Cao . Xiujuan Zhao
Received: 7 July 2020 / Accepted: 1 October 2020 Ó Springer Nature B.V. 2020
Abstract This study aims to explore the protective effects of quercetin against cadmium-induced nephrotoxicity utilizing metabolomics methods. Male Sprague–Dawley rats were randomly assigned to six groups: control, different dosages of quercetin (10 and 50 mg/kgbw, respectively), CdCl2 (4.89 mg/ kgbw) and different dosages quercetin plus CdCl2 groups. After 12 weeks, the kidneys were collected for metabolomics analysis and histopathology examination. In total, 11 metabolites were confirmed, the intensities of which significantly changed (up-regulated or down-regulated) compared with the control group (p \ 0.00067). These metabolites include xanthosine, uric acid (UA), guanidinosuccinic acid (GSA), hypoxanthine (Hyp), 12-hydroxyeicosatetraenoic acid (tetranor 12-HETE), taurocholic acid (TCA), hydroxyphenylacetylglycine (HPAG), deoxyinosine (DI), ATP, formiminoglutamic acid (FIGLU)
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10534-020-00260-2) contains supplementary material, which is available to authorized users. T. Guan Y. Xin K. Zheng R. Wang X. Zhang S. Jia S. Li C. Cao (&) X. Zhao (&) Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin 150081, Heilongjiang, China e-mail: [email protected] X. Zhao e-mail: [email protected]
and arachidonic acid (AA). When high-dose quercetin and cadmium were given to rats concurrently, the intensities of above metabolites significantly restored (p \ 0.0033 or p \ 0.00067). The results showed quercetin attenuated Cd-induced nephrotoxicity by regulating the metabolism of lipids, amino acids, and purine, inhibiting oxidative stress, and protecting kidney functions. Keywords Cadmium Quercetin Metabolomics UPLC-MS Nephrotoxicity
Introduction Cadmium (Cd) is a toxic heavy metal pollutant generally distributed in the environment, mainly existed in air, mining, smelting, electroplating, phosphate fertilizer and sludge (Tian et al. 2020; Turner 2019). Due to numerous industrial and human activities, environmental pollution is inevitable. For the non-occupational population, cadmium exposure is primarily through food, water, air, and dust (Bartholomew et al. 2020; Lamtai et al. 2020). In addition, smoking is another important way for the general population to contact cadmium. Cadmium, with an exceptionally long biological half-life of 10 to 30 years, is the most easily accumulated toxic substance in the body (Ja¨rup and Akesson 2009). Long-
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Biometals
term intake can cause different degrees of damages to the body. Studies have found that Cd exposure had many impacts on metabolism, such as mitochondrial energ
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