The Dysregulation of Eicosanoids and Bile Acids Correlates with Impaired Kidney Function and Renal Fibrosis in Chronic Renal Failure

Abstract

Chronic renal failure (CRF) is an irreversible deterioration of the renal functions that characterized by fluid electrolyte unbalance and metabolic-endocrine dysfunctions. Increasing evidence demonstrated that metabolic disturbances, especially dyslipidemia and profound changes in lipid and lipoprotein metabolism were involved in CRF. Identification of lipids associated with impaired kidney functions may play important roles in the understanding of biochemical mechanism and CRF treatment. Ultra-performance liquid chromatography coupled with high-definition mass spectrometry-based lipidomics was performed to identify important differential lipids in adenine-induced CRF rats and investigate the undergoing anti-fibrotic mechanism of Polyporus umbellatus (PPU) and ergone (ERG). Linear correlation analysis was performed between lipid species intensities and creatinine levels in serum. Adenine-induced rats exhibited declining kidney function and renal fibrosis. Compared with control rats, a panel of lipid species was identified in the serum of CRF rats. Our further study demonstrated that eight lipids, including leukotrienes and bile acids, presented a strong linear correlation with serum creatinine levels. In addition, receiver operating characteristics analysis showed that eight lipids exhibited excellent area under the curve for differentiating CRF from control rats, with high sensitivity and specificity. The aberrant changes of clinical biochemistry data and dysregulation of eight lipids could be significantly improved by the administration of PPU and ergone. In conclusion, CRF might be associated with the disturbance of leukotriene metabolism, bile acid metabolism and lysophospholipid metabolism. The levels of eicosanoids and bile acids could be used for indicating kidney function impairment in CRF. PPU could improve renal functions and either fully or partially reversed the levels of eicosanoids and bile acids.

1‐Hydroxypyrene mediates renal fibrosis through aryl hydrocarbon receptor signalling pathway

“…Previous untargeted metabolomic studies have compared patients with CKD with non‐CKD individuals using longitudinal cohorts from the European (McMahon et al, 2017; Sekula et al, 2016) and African–American populations and patients with end‐stage renal disease (Hocher & Adamski, 2017; Rhee et al, 2010). Accumulating endogenous metabolites have been identified in CKD (Chen, Cao, et al, 2019; Chen, Chen, et al, 2019; Feng, Cao, et al, 2019; Hocher & Adamski, 2017; Wang et al, 2019; Wang, Hu, et al, 2021; Wang, Wu, et al, 2021; Zhao, 2013). However, the biological function and pathophysiological mechanisms of these metabolites remain enigmatic.…”

Shenkang Injection and Its Three Anthraquinones Ameliorates Renal Fibrosis by Simultaneous Targeting IƙB/NF-ƙB and Keap1/Nrf2 Signaling Pathways

“…Male Sprague–Dawley rats (6–8 weeks old and weighing 180–210 g) were purchased from the Central Animal Breeding House of Xi’an Jiaotong University (Xi’an, Shaanxi, China). An adenine-induced CRF model was reproduced as described in detail previously ( Wang et al, 2021b ; Wang et al, 2021c ). In brief, the rats were divided into six groups ( n = 8/group) including control, adenine-induced CRF, SKI-treated group with CRF (CRF + SKI), chrysophanol-treated group with CRF (CRF + CHR), emodin-treated group with CRF (CRF + EMO), and rhein-treated group with CRF (CRF + RHE).…”

TGF-β/Smad Signaling Pathway in Tubulointerstitial Fibrosis

“…Traditional Chinese medicines (TCMs), a unique medical system with the remarkable feature of the use of multicomponent drugs, could hit multiple targets through multiple components ( Chen et al, 2018a ; Wang YN. et al, 2021 ).…”