PFOA and PFOS promote diabetic renal injury in vitro by impairing the metabolisms of amino acids and purines

Xun Gong, Chunxue Yang, Yanjun HONG, Chi Kong Arthur CHUNG*, Zongwei CAI

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Background: Environmental pollutants, perfluorooctanoic acid (PFOA)and perfluorooctane sulfonate (PFOS), are common surfactants in various consumer products. Epidemiological studies have demonstrated the association of diabetic kidney diseases with PFOA and PFOS. However, mechanisms of metabolic alterations involved are still unclear. Methods: Considering their involvement of glomerular hemodynamics, rat mesangial cells (MCs)are used as an in vitro model of diabetic kidney diseases for exposure to PFOS/PFOA under diabetic condition. Non-targeted metabolomics studies based on liquid chromatography-high resolution mass spectrometry were conducted to determine how PFOA/PFOS promoted fibrotic and proinflammatory responses in the MCs under diabetic condition. Results: Exposure of PFOA/PFOS (10 μM)increased oxidative stress and the levels of fibrotic and proinflammatory markers in MCs under diabetic condition. We demonstrated for the first time that PFOA and PFOS altered amino acid biosynthesis, citrate cycle, and purine metabolism in MCs under diabetic condition. Compared with diabetic condition, the exposure of PFOA and PFOS under diabetic condition more significantly altered the levels of 13 intracellular metabolites, including L-tyrosine, L-phenylalanine, L-arginine, L-tryptophan, AMP, ADP, UMP, inosine, and hypoxanthine, which have been reported to be related to kidney injury. In addition, PFOA/PFOS treatment significantly altered the expression levels of key enzymes involved in these metabolisms. Treatment with L-tyrosine, L-phenylalanine, L-arginine, and L-tryptophan reduced the levels of fibrotic and inflammatory markers induced by PFOA/PFOS. Conclusion: Our results suggest that under diabetic condition, exposure of PFOA or PFOS aggravated diabetic kidney injury in vitro by impairing metabolisms of amino acids and purines to induce more fibrosis and inflammation in MCs.

Original languageEnglish
Pages (from-to)72-86
Number of pages15
JournalScience of the Total Environment
Volume676
DOIs
Publication statusPublished - 1 Aug 2019

Scopus Subject Areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution

User-Defined Keywords

  • Amino acid metabolism
  • Fibrosis, diabetic kidney disease
  • PFOA, PFOS
  • Purine metabolism

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