Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 21, 2023

Diabetic nephropathy (DN) often leads to end-stage renal disease. Oxidative stress demonstrates a crucial act in the onset and progression of DN, which triggers various pathological processes while promoting activation inflammation forming vicious oxidative stress-inflammation cycle that induces podocyte injury, extracellular matrix accumulation, glomerulosclerosis, epithelial-mesenchymal transition, tubular atrophy, proteinuria. Conventional treatments for DN have limited efficacy. Polyphenols, as antioxidants, are widely used with multiple targets fewer adverse effects. This review reveals stress-associated led damage cells, including podocytes, endothelial mesangial epithelial cells. It potent antioxidant anti-inflammatory properties by targeting Nrf2, SIRT1, HMGB1, NF-κB, NLRP3 polyphenols, quercetin, resveratrol, curcumin, phenolic acid. However, there remains long way comprehensive understanding molecular mechanisms applications clinical therapy polyphenols.

Language: Английский

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Transition of acute kidney injury to chronic kidney disease: role of metabolic reprogramming

Metabolism, Journal Year: 2022, Volume and Issue: 131, P. 155194 - 155194

Published: March 26, 2022

Language: Английский

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Pharmacological Targeting of Mitochondria in Diabetic Kidney Disease

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 75(2), P. 250 - 262

Published: Dec. 12, 2022

Diabetic kidney disease (DKD) is the leading cause of end-stage renal (ESRD) in United States and many other countries. DKD occurs through a variety pathogenic processes that are part driven by hyperglycemia glomerular hypertension, to gradual loss function eventually progressing ESRD. In type 2 diabetes, chronic hyperfiltration leads proximal tubular dysfunction. Simultaneously, mitochondrial dysfunction early stages has been identified as key event development DKD. Clinical management for relies primarily on blood pressure glycemic control use numerous therapeutics slow progression. Because health over time, improve could be value different diseases. Increasing evidence supports idea targeting aspects dysfunction, such biogenesis dynamics, restores improves We will review effects current experimental homeostasis time.

Significance Statement

affects 20% 40% patients with diabetes limited treatment options. Mitochondrial progression DKD, pharmacologically restoring may potential therapeutic strategy preventing

Language: Английский

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Podocyte injury of diabetic nephropathy: Novel mechanism discovery and therapeutic prospects

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115670 - 115670

Published: Oct. 13, 2023

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, posing significant challenges in terms early prevention, clinical diagnosis, and treatment. Consequently, it has emerged as major contributor to end-stage renal disease. The glomerular filtration barrier, composed podocytes, endothelial cells, the basement membrane, plays vital role maintaining function. Disruptions podocyte function, including hypertrophy, shedding, reduced density, apoptosis, can impair integrity resulting elevated proteinuria, abnormal rate, increased creatinine levels. Hence, recent research increasingly focused on injury DN, with growing emphasis exploring therapeutic interventions targeting injury. Studies have revealed that factors such lipotoxicity, hemodynamic abnormalities, oxidative stress, mitochondrial dysfunction, impaired autophagy contribute This review aims summarize underlying mechanisms DN provide an overview current status regarding experimental drugs DN. findings presented herein may offer potential targets strategies for management associated

Language: Английский

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MK-886 protects against cardiac ischaemia/reperfusion injury by activating proteasome-Keap1-NRF2 signalling

Redox Biology, Journal Year: 2023, Volume and Issue: 62, P. 102706 - 102706

Published: April 20, 2023

Oxidative stress is considered a key factor contributing to the initiation and development of cardiac injury following ischaemia‒reperfusion (I/R). Arachidonate 5-lipoxygenase (ALOX5) rate-limiting enzyme for leukotriene biosynthesis. MK-886 an inhibitor ALOX5 that exhibits anti-inflammatory antioxidant activities. However, significance in preventing I/R-mediated underlying mechanism remain unclear. Cardiac I/R model was produced by ligation/release left anterior descending artery. (20 mg/kg) administered intraperitoneally into mice at 1 24 h before I/R. Our results indicated treatment significantly attenuated contractile dysfunction decreased infarct area, myocyte apoptosis, oxidative accompanied with reduction Kelch-like ECH-associated protein (keap1) upregulation nuclear erythroid 2-related 2 (NRF2). Conversely, administration proteasome epoxomicin NRF2 ML385 greatly abrogated MK-886-mediated cardioprotection after injury. Mechanistically, enhanced expression immunoproteasome subunit β5i, which interacted keap1 its degradation, leading activation NRF2-dependent response improvement mitochondrial fusion-fission balance I/R-treated heart. In summary, our present findings could protect heart against highlight may represent promising therapeutic candidate ischaemic disease.

Language: Английский

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Reduction of anaerobic glycolysis contributes to angiotensin II-induced podocyte injury with foot process effacement

Kidney International, Journal Year: 2023, Volume and Issue: 103(4), P. 735 - 748

Published: Jan. 31, 2023

Language: Английский

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Single-cell atlas reveals multi-faced responses of losartan on tubular mitochondria in diabetic kidney disease

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 21, 2025

Mitochondria are crucial to the function of renal tubular cells, and their dynamic perturbation in many aspects is an important mechanism diabetic kidney disease (DKD). Single-nucleus RNA sequencing (snRNA-seq) technology a high-throughput analysis technique for at level single cell nucleus. Here, our DKD mouse single-cell conveys more comprehensive mitochondrial profile, which helps us further understand therapeutic response this unique organelle family drugs. After high fat diet (HFD), mice were intraperitoneally injected with streptozotocin (STZ) induce DKD, then divided into three subsets: CON (healthy) subset, (vehicle) LST (losartan; 25 mg/kg/day) subset. Divide HK-2 LG (low glucose; 5 mM) HG (high 30 + 1 µ M) subsets. snRNA-seq was performed on tissues subset mice. To reveal effects losartan gene pathway changes mitochondria, Gene Ontology (GO) enrichment GSEA/GSVA scoring analyze specific proximal (PT) mitochondria treatment, including key events homeostasis such as morphology, dynamics, mitophagy, autophagic flux, respiratory chain, apoptosis, ROS generation. Preliminary validation through vitro vivo experiments, observation morphology dynamics using probes Mitotracker Red, evaluation effect electron microscopy, laser confocal immunofluorescence, Western blotting. Detection flux cells by transfecting Ad-mCherry-GFP-LC3B dual fluorescence labeled adenovirus. Various fluorescent energy detector used detect ROS, respiration mitochondrion. Through atlas kidneys, it found that treatment significantly increased percentage PT cells. differentially expressed genes showed autophagy mitochondrion pathway. Further GSEA GSVA revealed mitophagy other events, production, membrane potential, adenosine triphosphate (ATP) synthesis, involved protective thereby improving homeostasis. Consistent results also obtained cellular experiments. In addition, we highlighted subpopulation phenotype data, preliminarily validated co-localization expression Pink1 Gclc specimens patients treated losartan. Our research suggests scRNA-seq can reflect multifaceted landscape after drug these findings may provide new targets therapy level.

Language: Английский

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Mitochondrial Oxidative Stress and Cell Death in Podocytopathies

Biomolecules, Journal Year: 2022, Volume and Issue: 12(3), P. 403 - 403

Published: March 4, 2022

Podocytopathies are kidney diseases that driven by podocyte injury with proteinuria and proteinuria-related symptoms as the main clinical presentations. Albeit podocytopathies major contributors to end-stage disease, underlying molecular mechanisms of remain be elucidated. Mitochondrial oxidative stress is associated diseases, increasing evidence suggests plays a vital role in pathogenesis podocytopathies. Accumulating has placed mitochondrial focus cell death research. Excessive generated reactive oxygen species over antioxidant defense under pathological conditions lead damage cellular components regulate podocyte. Conversely, exogenous antioxidants can protect from death. This review provides an overview discusses its podocyte, aiming identify novel targets improve treatment patients

Language: Английский

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Keap1-independent Nrf2 regulation: a novel therapeutic target for treating kidney disease

Redox Biology, Journal Year: 2025, Volume and Issue: 82, P. 103593 - 103593

Published: March 12, 2025

Language: Английский

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Pharmacological significance of MitoQ in ameliorating mitochondria-related diseases

Advances in Redox Research, Journal Year: 2022, Volume and Issue: 5, P. 100037 - 100037

Published: May 11, 2022

The Mitochondria is a critical sub-cellular organelle that plays an integral part in normal cellular process. Besides ATP production, the mitochondria participate various key processes such as cell signaling, epigenetic regulation leading to proliferation, migration, apoptosis, differentiation, and autophagy – highlighting their importance health. However, mitochondrial dysfunction has serious organismal consequences, playing roles pathophysiology of many diseases, including neurodegenerative disorders, cardiovascular cancer, pulmonary liver diseases. In recent years, spurred surge interest developing mitochondria-targeted therapies. MitoQ selective antioxidant concentrates prevents oxidative damage mitochondria. therapeutic relevance been studied diseased conditions determine its efficacy either slowing disease progression or alleviating symptoms. this review, we discussed selected diseases benefit numerous studies.

Language: Английский

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