Abstract | BACKGROUND: The kidney plays a central role in elimination of metabolic waste products and regulation of low-molecular weight metabolites via glomerular filtration, tubular secretion and reabsorption. Disruption of these processes results in profound changes in the biochemical milieu of the body fluids, which contribute to complications of chronic kidney disease (CKD) by inducing cytotoxicity and inflammation. Insight into the changes of the composition of metabolites and dysregulation of target genes and proteins enhances the understanding of the pathophysiology of CKD and its complications, and the development of novel therapeutic strategies. Chronic interstitial nephropathy is a common cause of CKD. The present study was designed to determine the effect of chronic interstitial nephropathy on the composition of serum metabolites and regulation of oxidative, inflammatory, fibrotic and cytoprotective pathways. METHODS: Male Sprague-Dawley rats were randomized to the CKD and control groups ( n = 8/group). CKD was induced by administration of adenine (200 mg/kg body weight/day) by oral gavage for 3 weeks. The control group was treated with the vehicle alone. The animals were then observed for an additional 3 weeks, at which point they were sacrificed and kidney and serum samples were collected. Serum metabolomic and lipidomic analyses were performed using ultra-performance liquid chromatography-quadrupole time-of-flight high-definition mass spectrometry. Kidney tissues were processed for histological and molecular biochemical analyses. RESULTS: CONCLUSIONS: Advanced CKD in rats with adenine-induced chronic interstitial nephropathy results in profound changes in the serum metabolome, activation of inflammatory, oxidative and fibrotic pathways, and suppression of cytoprotective and antioxidant pathways.
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Authors | Dan-Qian Chen, Hua Chen, Lin Chen, Nosratola D Vaziri, Ming Wang, Xiang-Ri Li, Ying-Yong Zhao |
Journal | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
(Nephrol Dial Transplant)
Vol. 32
Issue 7
Pg. 1154-1166
(Jul 01 2017)
ISSN: 1460-2385 [Electronic] England |
PMID | 28339984
(Publication Type: Journal Article)
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Copyright | © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. |
Chemical References |
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Topics |
- Animals
- Biomarkers
(metabolism)
- Fatty Acids
(metabolism)
- Lipid Metabolism
- Male
- Metabolome
- Metabolomics
(methods)
- Phenotype
- Rats
- Rats, Sprague-Dawley
- Renal Insufficiency, Chronic
(metabolism, physiopathology)
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