The role of eicosanoids in renal diseases – potential therapeutic possibilities

Fijałkowski, Maciej; Stępniewska, Joanna; Domański, Maciej; Ciechanowski, Kazimierz; Gołembiewska, Edyta

doi:10.18388/abp.2018_2609

Cited by 5 publications

(4 citation statements)

References 69 publications

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“…A Bar chart of the top 30 significant GO terms from the targets. B-E GOChord to donate the relationship between GO terms and potential targets which are related to immunomodulatory and inflammatory effects membrane phospholipids, is being considered biomarkers for detecting acute kidney injury, nephrotoxicity, glomerulonephritis, and early stages of diabetic nephropathy because of their participation in inflammatory processes and in oxidative stress (Fijalkowski et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of Jianpi Qushi Huayu Formula in the treatment of chronic glomerulonephritis based on network pharmacology

Liu

Gao

Qin

et al. 2021

Naunyn-Schmiedeberg's Arch Pharmacol

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This study was to explore the effective components, potential targets, and pathways of Jianpi Qushi Huayu Formula (JQHF) for the treatment of chronic glomerulonephritics (CGN). First, the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), GeneCards, and OMIM databases were used to collect the major active components of JQHF and potential therapeutic targets of CGN. Then, functional enrichment analysis was performed to clarify the mechanisms of the JQHF on CGN. Subsequently, molecular docking was simulated to assess the binding ability of key targets and major active components. Finally, quantitative real-time PCR and western blot were performed for experimental verification of cells in vitro. A total of 55 active ingredients contained and 220 putative identified targets were screened from JQHF, of which 112 overlapped with the targets of CGN and were considered potential therapeutic targets. Then, we found quercetin and kaempferol are two key ingredients of JQHF, which may act on the top 10 screened targets of PPI, affecting CGN through related signal transduction pathways. Subsequently, molecular docking predicted that quercetin and kaempferol bind firm with the top 10 core targets of PPI. Further experiment verified some results and showed that JQHF has protected glomerular mesangial cells from lipopolysaccharide-induced inflammation by inhibiting expressions of IL6, TNF-α, and AKT1, and activating expressions of VEGFA. Based on network pharmacology, we explored the multi-component, multi-target, and multi-pathway characteristics of JQHF in treating CGN, and found that JQHF could act on IL6, TNF-α, VEGFA, and AKT1 to exert the effect of anti-CGN, which provided new ideas and methods for further research on the mechanism of JQHF in treating CGN.

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Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of Jianpi Qushi Huayu Formula in the treatment of chronic glomerulonephritis based on network pharmacology

Liu

Gao

Qin

et al. 2021

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Several of the enriched gene sets in this study have been suggested to mediate renal dysfunction. Eicosanoids and arachidonic metabolism play major roles in kidney inflammation and have been shown to predict chronic kidney disease progression in patients [ 44 , 45 , 46 ]. Extracellular matrix turnover plays a role in aberrant wound healing and fibrosis, which is a hallmark of kidney disease.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis of the Differential Nephrotoxicity of Diverse Brominated Flame Retardants in Rat and Human Renal Cells

Barnett

Kramer

Buerger

et al. 2021

IJMS

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Brominated flame retardants (BFRs) are environmentally persistent, are detected in humans, and some have been banned due to their potential toxicity. BFRs are developmental neurotoxicants and endocrine disruptors; however, few studies have explored their potential nephrotoxicity. We addressed this gap in the literature by determining the toxicity of three different BFRs (tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD), and tetrabromodiphenyl ether (BDE-47)) in rat (NRK 52E) and human (HK-2 and RPTEC) tubular epithelial cells. All compounds induced time- and concentration-dependent toxicity based on decreases in MTT staining and changes in cell and nuclear morphology. The toxicity of BFRs was chemical- and cell-dependent, and human cells were more susceptible to all three BFRs based on IC50s after 48 h exposure. BFRs also had chemical- and cell-dependent effects on apoptosis as measured by increases in annexin V and PI staining. The molecular mechanisms mediating this toxicity were investigated using RNA sequencing. Principal components analysis supported the hypothesis that BFRs induce different transcriptional changes in rat and human cells. Furthermore, BFRs only shared nine differentially expressed genes in rat cells and five in human cells. Gene set enrichment analysis demonstrated chemical- and cell-dependent effects; however, some commonalities were also observed. Namely, gene sets associated with extracellular matrix turnover, the coagulation cascade, and the SNS-related adrenal cortex response were enriched across all cell lines and BFR treatments. Taken together, these data support the hypothesis that BFRs induce differential toxicity in rat and human renal cell lines that is mediated by differential changes in gene expression.

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“…Over the years, experiments have indicated that lipids and lipid-derived metabolites were not only involved in inflammatory processes and oxidative stress but also played an important role in the physiological and pathological processes of the kidney. Arachidonic acid (AA) is a component of cell membrane phospholipids, which makes us believe that its connection to the kidney is also related to the improvement of inflammation and reduction of oxidative stress [24]. Studies have found out that low linolenic and linoleic acid consumption are associated with the chronic kidney disease in patients with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Serum Metabolic Biomarkers of Diabetic Kidney Disease: A Widely Targeted Metabolomics Study

Zhang

Zuo

Dong

et al. 2020

Journal of Diabetes Research

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Background and Objectives. Diabetic kidney disease is a leading cause of chronic kidney disease and end-stage renal disease across the world. Early identification of DKD is vitally important for the effective prevention and control of it. However, the available indicators are doubtful in the early diagnosis of DKD. This study is aimed at determining novel sensitive and specific biomarkers to distinguish DKD from their counterparts effectively based on the widely targeted metabolomics approach. Materials and Method. This case-control study involved 44 T2DM patients. Among them, 24 participants with DKD were defined as the cases and another 20 without DKD were defined as the controls. The ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry system was applied for the assessment of the serum metabolic profiles. Comprehensive analysis of metabolomics characteristics was conducted to detect the candidate metabolic biomarkers and assess their capability and feasibility. Result. A total of 11 differential metabolites, including Hexadecanoic Acid (C16:0), Linolelaidic Acid (C18:2N6T), Linoleic Acid (C18:2N6C), Trans-4-Hydroxy-L-Proline, 6-Aminocaproic Acid, L-Dihydroorotic Acid, 6-Methylmercaptopurine, Piperidine, Azoxystrobin Acid, Lysopc 20:4, and Cuminaldehyde, were determined as the potential biomarkers for the DKD early identification, based on the multivariable generalized linear regression model and receiver operating characteristic analysis. Conclusion. Serum metabolites might act as sensitive and specific biomarkers for DKD early detection. Further longitudinal studies are needed to confirm our findings.

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The role of eicosanoids in renal diseases – potential therapeutic possibilities

Cited by 5 publications

References 69 publications

Exploring the mechanism of Jianpi Qushi Huayu Formula in the treatment of chronic glomerulonephritis based on network pharmacology

Exploring the mechanism of Jianpi Qushi Huayu Formula in the treatment of chronic glomerulonephritis based on network pharmacology

Transcriptomic Analysis of the Differential Nephrotoxicity of Diverse Brominated Flame Retardants in Rat and Human Renal Cells

Identification of Potential Serum Metabolic Biomarkers of Diabetic Kidney Disease: A Widely Targeted Metabolomics Study

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