Metabolomics analysis of the effects of quercetin on renal toxicity induced by cadmium exposure in rats

Biometals. 2021 Feb;34(1):33-48. doi: 10.1007/s10534-020-00260-2. Epub 2020 Oct 8.

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/kg·bw, respectively), CdCl2 (4.89 mg/kg·bw) 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) 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; Metabolomics; Nephrotoxicity; Quercetin; UPLC-MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadmium / toxicity
  • Dose-Response Relationship, Drug
  • Injections, Intraperitoneal
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney / pathology
  • Male
  • Metabolomics*
  • Oxidative Stress / drug effects
  • Protective Agents / administration & dosage
  • Protective Agents / metabolism*
  • Protective Agents / pharmacology
  • Quercetin / administration & dosage
  • Quercetin / metabolism*
  • Quercetin / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Protective Agents
  • Cadmium
  • Quercetin