Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment

BioMed Research International, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 17

Published: July 8, 2021

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Chronic hyperglycemia and high blood pressure are main risk factors for development DN. In general, screening microalbuminuria should be performed annually, starting 5 years after diagnosis in type 1 diabetes at annually thereafter 2 diabetes. Standard therapy glucose control using renin-angiotensin system blockade, targeting $\text{A}1\text{c}<7\%$ , <130/80 mmHg. Regression albuminuria remains an important therapeutic goal. However, there problems treatment nonproteinuric DN (NP-DN), which does not follow classic pattern fact, prevalence continues to increase, additional needed prevent or ameliorate condition. addition conventional therapies, vitamin D receptor activators, incretin-related drugs, therapies that target inflammation may also promising prevention progression. This review focuses on role oxidative stress pathogenesis DN, approaches NP-DN, current emerging interventions.

Language: Английский

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Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases

Frontiers in Chemistry, Journal Year: 2023, Volume and Issue: 11

Published: May 10, 2023

Introduction: Free radicals are reactive oxygen species that constantly circulate through the body and occur as a side effect of many reactions take place in human body. Under normal conditions, they removed from by antioxidant processes. If these natural mechanisms disrupted, accumulate excess contribute to development diseases. Methodology: Relevant recent information on oxidative stress, free radicals, species, synthetic antioxidants was collected researching electronic databases such PubMed / Medline, Web Science, Science Direct. Results: According analysed studies, this comprehensive review provided update their impact pathophysiology Discussion: To counteract condition must be external sources supplement defense mechanism internally. Because therapeutic potential origin, medicinal plants have been reported main source phytocompounds. Some non-enzymatic phytocompounds flavonoids, polyphenols, glutathione, along with some vitamins possess strong activities vivo vitro studies. Thus, present describes, brief, overview stress-directed cellular damage unction dietary management different The limitations correlating activity foods health were also discussed.

Language: Английский

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NAFLD as a driver of chronic kidney disease

Journal of Hepatology, Journal Year: 2020, Volume and Issue: 72(4), P. 785 - 801

Published: Feb. 12, 2020

Language: Английский

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Oxidative Stress in the Pathophysiology of Kidney Disease: Implications for Noninvasive Monitoring and Identification of Biomarkers

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 11

Published: Jan. 28, 2020

Kidney disease represents a serious global health problem. One of the main concerns is its late diagnosis, only feasible in progressed state. The lack clinical manifestation early stages and fact that commonly measured parameters renal function are markedly reduced during advanced cause. Changes at molecular level kidney tissue occur even before nitrogenous substances, such as creatinine urea, start to accumulate blood. Renal proximal tubules contain large number mitochondria critical for energy-demanding process reabsorption water solutes. Mitochondria largest producers oxygen radicals, which, turn, increase susceptibility kidneys oxidative stress-induced damage. Free radicals prooxidants produced acute or chronic injury may further aggravate course play role pathogenesis subsequent complications. Prevention might be solution CKD, but patients often reluctant undergo preventive examinations. Noninvasive markers possibility obtain samples home help compliance. This review will provide an overview possible uses status noninvasive biofluids with disease.

Language: Английский

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Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9352 - 9352

Published: May 27, 2023

This review focuses on the multiple and reciprocal relationships that exist between oxidative stress, hyperglycemia diabetes related metabolic disorders. Human metabolism uses most of consumed glucose under aerobic conditions. Oxygen is needed in mitochondria to obtain energy, as well for action microsomal oxidases cytosolic pro-oxidant enzymes. relentlessly generates a certain amount reactive oxygen species (ROS). Although ROS are intracellular signals necessary some physiological processes, their accumulation leads hyperglycemia, progressive resistance insulin. A cellular versus an antioxidant equilibrium would regulate levels, but pro-inflammatory conditions feed back each other relevance interconnections tends increase those Hyperglycemia promotes collateral through protein kinase C, polyols hexosamine routes. In addition, it also facilitates spontaneous auto-oxidation formation advanced glycation end products (AGEs), which turn interact with receptors (RAGE). The mentioned processes undermine structures, finally giving place progressively greater degree stress further alterations, complications. NFκB major transcription factor involved expression mediators, while Nrf2 regulating response. FoxO equilibrium, its role controversial. summarizes key factors linking diverse routes enhanced vice versa, emphasizing desirable balance proteins.

Language: Английский

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Polysulfide-mediated sulfhydration of SIRT1 prevents diabetic nephropathy by suppressing phosphorylation and acetylation of p65 NF-κB and STAT3

Redox Biology, Journal Year: 2020, Volume and Issue: 38, P. 101813 - 101813

Published: Nov. 25, 2020

Diabetic kidney disease is known as a major cause of chronic and end stage renal disease. Polysulfides, class chemical agents with chain sulfur atoms, are found to confer protective effects in acute injury. However, whether polysulfide donor, sodium tetrasulfide (Na2S4), confers against diabetic nephropathy remains unclear. Our results showed that Na2S4 treatment ameliorated dysfunctional histological damage kidneys through inhibiting the overproduction inflammation cytokine reactive oxygen species (ROS), well attenuating fibrosis cell apoptosis. Additionally, upregulated phosphorylation acetylation levels p65 nuclear factor κB (p65 NF-κB) signal transducer activator transcription 3 (STAT3) were abrogated by sirtuin-1 (SIRT1)-dependent manner. In tubular epithelial cells, directly sulfhydrated SIRT1 at two conserved CXXC domains (Cys371/374; Cys395/398), then induced dephosphorylation deacetylation its targeted proteins including NF-κB STAT3, thereby reducing high glucose (HG)-caused oxidative stress, apoptosis, response epithelial-to-mesenchymal transition (EMT) progression. Most importantly, inactivation specific inhibitor EX-527, small interfering RNA (siRNA), de-sulfhydration reagent dithiothreitol (DTT), or mutation Cys371/374 Cys395/398 sites abolished on insulting. These reveal polysulfides may attenuate lesions via STAT3 phosphorylation/acetylation sulfhydrating SIRT1.

Language: Английский

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AGE/RAGE in diabetic kidney disease and ageing kidney

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 171, P. 260 - 271

Published: May 18, 2021

Language: Английский

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Mechanistic Pathogenesis of Endothelial Dysfunction in Diabetic Nephropathy and Retinopathy

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: May 25, 2022

Diabetic nephropathy (DN) and diabetic retinopathy (DR) are microvascular complications of diabetes. Microvascular endothelial cells thought to be the major targets hyperglycemic injury. In microvasculature, intracellular hyperglycemia causes damages vascular endothelium, via multiple pathophysiological process consist inflammation, cell crosstalk with podocytes/pericytes exosomes. addition, DN DR diseases development involved in several critical regulators including adhesion molecules (CAMs), growth factor (VEGF) family Notch signal. The present review attempts gain a deeper understanding pathogenesis complexities underlying dysfunction diabetes retinopathy, contributing new mechanistic therapeutic strategies against diabetes-induced dysfunction.

Language: Английский

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MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against diabetic nephropathy in rats through facilitating M2 macrophage polarization

Stem Cell Research & Therapy, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 27, 2022

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and common cause end-stage renal disease (ESRD). Mesenchymal stem cells (MSCs) possess potent anti-inflammatory immunomodulatory properties, which render them an attractive therapeutic tool for tissue damage inflammation.This study was designed to determine the protective effects underlying mechanisms human umbilical cord-derived MSCs (UC-MSCs) on streptozotocin-induced DN. Renal function histological staining were used evaluate kidney damage. RNA high-throughput sequencing rat UCMSC-derived exosomes identify critical miRNAs. Co-cultivation macrophage cell lines UC-MSCs-derived conditional medium assess involvement polarization signaling.UC-MSC administration significantly improved function, reduced local systemic inflammatory cytokine levels, attenuated infiltration into in DN rats. Moreover, UC-MSCs shifted from pro-inflammatory M1 M2 phenotype. Mechanistically, miR-146a-5p downregulated negatively correlated with injury rats as determined through sequencing. Importantly, promoted by inhibiting tumor necrosis factor receptor-associated factor-6 (TRAF6)/signal transducer activator transcription (STAT1) signaling pathway. Furthermore, modification enhanced efficacy anti-inflammation improvement.Collectively, our findings demonstrate that have potential restore facilitating targeting TRAF6. This would pave way use miRNA-modified therapy diseases.

Language: Английский

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NADPH oxidase family proteins: signaling dynamics to disease management

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(6), P. 660 - 686

Published: May 18, 2022

Language: Английский

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