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

Xun Gong; Chunxue Yang; Yanjun Hong; Arthur C K Chung; Zongwei Cai

doi:10.1016/j.scitotenv.2019.04.208

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

Sci Total Environ. 2019 Aug 1:676:72-86. doi: 10.1016/j.scitotenv.2019.04.208. Epub 2019 Apr 16.

Authors

Xun Gong¹, Chunxue Yang², Yanjun Hong¹, Arthur C K Chung³, Zongwei Cai¹

Affiliations

¹ State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China; HKBU Institute for Research and Continuing Education, Shenzhen, China.
² State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China.
³ State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China; HKBU Institute for Research and Continuing Education, Shenzhen, China. Electronic address: chungack@hkbu.edu.hk.

PMID: 31029902
DOI: 10.1016/j.scitotenv.2019.04.208

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.

Keywords: Amino acid metabolism; Fibrosis, diabetic kidney disease; PFOA, PFOS; Purine metabolism.

MeSH terms

Alkanesulfonic Acids / toxicity*
Amino Acids / metabolism*
Animals
Caprylates / toxicity*
Diabetes Mellitus / metabolism
Environmental Pollutants
Fluorocarbons / toxicity*
Kidney / metabolism
Purines / metabolism*
Rats
Toxicity Tests

Substances

Alkanesulfonic Acids
Amino Acids
Caprylates
Environmental Pollutants
Fluorocarbons
Purines
perfluorooctanoic acid
perfluorooctane sulfonic acid