European Journal of Pharmacology, Год журнала: 2022, Номер 920, С. 174846 - 174846
Опубликована: Фев. 22, 2022
Язык: Английский
Frontiers in Immunology, Год журнала: 2023, Номер 14
Опубликована: Июль 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.
Язык: Английский
Процитировано
122
Metabolism, Год журнала: 2022, Номер 131, С. 155194 - 155194
Опубликована: Март 26, 2022
Язык: Английский
Процитировано
95
Pharmacological Reviews, Год журнала: 2022, Номер 75(2), С. 250 - 262
Опубликована: Дек. 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.
Язык: Английский
Процитировано
59
Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 168, С. 115670 - 115670
Опубликована: Окт. 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
Язык: Английский
Процитировано
40
Redox Biology, Год журнала: 2023, Номер 62, С. 102706 - 102706
Опубликована: Апрель 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.
Язык: Английский
Процитировано
31
Kidney International, Год журнала: 2023, Номер 103(4), С. 735 - 748
Опубликована: Янв. 31, 2023
Язык: Английский
Процитировано
28
Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)
Опубликована: Янв. 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.
Язык: Английский
Процитировано
1
Biomolecules, Год журнала: 2022, Номер 12(3), С. 403 - 403
Опубликована: Март 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
Язык: Английский
Процитировано
26
Redox Biology, Год журнала: 2025, Номер 82, С. 103593 - 103593
Опубликована: Март 12, 2025
Язык: Английский
Процитировано
0
Advances in Redox Research, Год журнала: 2022, Номер 5, С. 100037 - 100037
Опубликована: Май 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.
Язык: Английский
Процитировано
22