Metabonomics revealed xanthine oxidase-induced oxidative stress and inflammation in the pathogenesis of diabetic nephropathy

Liu, Jingping; Wang, Chengshi; Liu, Fang; Liu, Yanrong; Cheng, Jun

doi:10.1007/s00216-015-8481-0

Cited by 77 publications

(66 citation statements)

References 35 publications

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“…To show the metabolic changes associated with DN, Liu analyzed the serum, urine, and renal extracts obtained from control and STZ‐induced DN rats by 1 H NMR‐based metabolomics and multivariate data analysis. A significant difference between control and DN rats was shown in their metabolic profiles, and several important DN‐related metabolites, including increased levels of urine allantoin and serum uric acid, in the DN rats were identified, suggesting that disturbed purine metabolism might be involved in DN.…”

Section: Application Of Metabolomics In Diabetic Complicationsmentioning

confidence: 99%

Metabolomics window into diabetic complications

Qiao

Shi

et al. 2017

J of Diabetes Invest

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Diabetes has become a major global health problem. The elucidation of characteristic metabolic alterations during the diabetic progression is critical for better understanding its pathogenesis, and identifying potential biomarkers and drug targets. Metabolomics is a promising tool to reveal the metabolic changes and the underlying mechanism involved in the pathogenesis of diabetic complications. The present review provides an update on the application of metabolomics in diabetic complications, including diabetic coronary artery disease, diabetic nephropathy, diabetic retinopathy and diabetic neuropathy, and this review provides notes on the prevention and prediction of diabetic complications.

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Section: Application Of Metabolomics In Diabetic Complicationsmentioning

confidence: 99%

Metabolomics window into diabetic complications

Qiao

Shi

et al. 2017

J of Diabetes Invest

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“…1 H NMR-based analysis of serum, urine, and renal extracts from streptozotocin-induced diabetic rats revealed dramatic increases in uric acid and its oxidized form allantoin, whose production is driven by ROS. 88 Both metabolites are involved in the development of microalbuminuria and inflammation. Dysregulated purine metabolism and excessive generation of allantoin was also recently implicated in the pathogenesis of ischemic retinopathy (see Retinopathy section), and may hold potential as a therapeutic route for multiple diabetic complications.…”

Section: Nephropathymentioning

confidence: 99%

Metabolomics in diabetic complications

Filla

Edwards

2016

Mol. BioSyst.

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With a global prevalence of 9%, diabetes is the direct cause of millions of deaths each year and is quickly becoming a health crisis. Major long-term complications of diabetes arise from persistent oxidative stress and dysfunction in multiple metabolic pathways. The most serious complications involve vascular damage and include cardiovascular disease as well as microvascular disorders such as nephropathy, neuropathy, and retinopathy. Current clinical analyses like glycated hemoglobin and plasma glucose measurements hold some value as prognostic indicators of the severity of complications, but investigations into the underlying pathophysiology are still lacking. Advancements in biotechnology hold the key to uncovering new pathways and establishing therapeutic targets. Metabolomics, the study of small endogenous molecules, is a powerful toolset for studying pathophysiological processes and has been used to elucidate metabolic signatures of diabetes in various biological systems. Current challenges in the field involve correlating these biomarkers to specific complications to provide a better prediction of future risk and disease progression. This review will highlight the progress that has been made in the field of metabolomics including technological advancements, the identification of potential biomarkers, and metabolic pathways relevant to macro- and microvascular diabetic complications.

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“…Recently, studies have demonstrated that oxidative stress is an important pathogenic factor of diabetic complications including nephropathy (12)(13)(14). Oxidative stress and inflammation are linked, as each begets and amplifies the other.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model

et al. 2016

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Abstract. The aim of the present study was to investigate the renoprotective effects of isorhamnetin (ISO) in type 2 diabetic rats and its effects on the nuclear factor-κB (NF-κB) signaling pathway, which is associated with diabetic nephropathy. The type 2 diabetic rat model was established by a high-fat diet plus streptozocin injection and the rats were subsequently treated with two dosages of ISO, respectively. The levels of blood glucose were determined. Urinary osteopontin, kidney injury molecule-1 (KIM-1) and albumin were measured to evaluate the renal function of the rats. Renal NF-κB signaling activity was assessed by measuring the levels of NF-κB p65, phospho-NF-κB p65, inhibitor of NF-κB (IκBα) and phospho-IκBα, and the NF-κB p65 DNA-binding activity. Downstream inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-β1 (TGF-β1)] of the NF-κB signaling pathway were investigated to evaluate the renal inflammatory response. Renal levels of malondialdehyde and total superoxide dismutase were detected to access the oxidative stress. Furthermore, glomerular mesangial cells (GMCs) were treated with lipopolysaccharide and ISO. In the cellular experiment, the NF-κB signaling activity, levels of TNF-α, IL-1β, IL-6, ICAM-1 and TGF-β1, and oxidative stress were also investigated. The results showed that ISO decreased the levels of urinary osteopontin, KIM-1 and albumin. ISO also inhibited the NF-κB signaling activity, decreased the production of inflammatory mediators and attenuated oxidative stress in diabetic rats and GMCs. The present investigations revealed that ISO had ameliorative effects on diabetes-induced renal damage and the activity may be associated with the negative regulation of NF-κB signaling pathway.

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Metabonomics revealed xanthine oxidase-induced oxidative stress and inflammation in the pathogenesis of diabetic nephropathy

Cited by 77 publications

References 35 publications

Metabolomics window into diabetic complications

Metabolomics window into diabetic complications

Metabolomics in diabetic complications

Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model

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