Klotho, Oxidative Stress, and Mitochondrial Damage in Kidney Disease

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 239 - 239

Published: Jan. 20, 2023

Reducing oxidative stress stands at the center of a prevention and control strategy for mitigating cellular senescence aging. Kidney disease is characterized by premature aging syndrome, to find modulator targeting against stress, mitochondrial dysfunction, in kidney cells could be great significance prevent progression this disease. This review focuses on pathogenic mechanisms related appearance damage dysfunction In scenario, anti-aging Klotho protein plays crucial role modulating signaling pathways involving manganese-containing superoxide dismutase (Mn-SOD) transcription factors FoxO Nrf2, known antioxidant systems, other function regulators, such as uncoupling 1 (UCP1), B-cell lymphoma-2 (BCL-2), Wnt/β-catenin, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), factor EB, (TFEB), (PPAR-gamma). Therefore, postulated very promising new target future therapeutic strategies mitochondria abnormalities, patients.

Language: Английский

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Electroacupuncture attenuates ferroptosis by promoting Nrf2 nuclear translocation and activating Nrf2/SLC7A11/GPX4 pathway in ischemic stroke

Chinese Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 4, 2025

Abstract Objective Electroacupuncture has been shown to play a neuroprotective role following ischemic stroke, but the underlying mechanism remains poorly understood. Ferroptosis key in injury process. In present study, we wanted explore whether electroacupuncture could inhibit ferroptosis by promoting nuclear factor erythroid-2-related 2 (Nrf2) translocation. Methods The stroke model was established middle cerebral artery occlusion/reperfusion (MCAO/R) adult rats. These rats have randomly divided into EA + MCAO/R group, Brusatol group (the inhibitor of Nrf2), and DMSO Sham group. received intervention 24 h after modeling for 7 consecutive days. behavioral function evaluated Neurologic severity score (NSS), Garcia score, Foot-fault Test, Rotarod Test. infarct volume detected TTC staining, neuronal damage observed Nissl staining. levels Fe 2+ , reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) were measured ELISA. immunofluorescence Western blotting used detect expression Total Nrf2, p-Nrf2, Nuclear Cytoplasmic essential proteins, including glutathione peroxidase 4 (GPX4), solute carrier family member 11 (SLC7A11) ferritin heavy chain 1 (FTH1). mitochondria transmission electron microscopy (TEM). Results improved neurological deficits MCAO/R, decreased brain volume, alleviated damage, inhibited ROS, MDA accumulation, increased SOD levels, GPX4, SLC7A11 FTH1, rescued injured mitochondria. Especially, found that up-regulated promoted phosphorylation Nrf2 translocation, However, reversed effect electroacupuncture. Conclusion can alleviate I/R injury-induced It is expected these data will provide novel insights mechanisms protecting against potential targets stroke. Graphical

Language: Английский

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Pharmacological activities and pharmacokinetics of liquiritin: A review

Journal of Ethnopharmacology, Journal Year: 2022, Volume and Issue: 293, P. 115257 - 115257

Published: April 5, 2022

Language: Английский

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DCA Protects against Oxidation Injury Attributed to Cerebral Ischemia‐Reperfusion by Regulating Glycolysis through PDK2‐PDH‐Nrf2 Axis

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Cerebral ischemic stroke (IS) is still a difficult problem to be solved; energy metabolism failure one of the main factors causing mitochondrion dysfunction and oxidation stress damage within pathogenesis cerebral ischemia, which produces considerable reactive oxygen species (ROS) opens blood-brain barrier. Dichloroacetic acid (DCA) can inhibit pyruvate dehydrogenase kinase (PDK). Moreover, DCA has been indicated with capability increasing mitochondrial uptake promoting glucose in course glycolysis, thereby improving activity (PDH). As result, flow promoted into tricarboxylic cycle expedite ATP production. protective effect on IS brain ischemia/reperfusion (I/R) injury, but specific mechanism remains unclear. This study adopted transient middle artery occlusion (MCAO) mouse model for simulating I/R injury mice. We investigated by regulates glycolysis protects oxidative induced through PDK2-PDH-Nrf2 axis. from results this study, may improve reduce neuronal death, barrier, promote recovery inhibiting PDK2 activating PDH. Additionally, noticeably elevated neurological score reduced infarct volume, water content, necrotic neurons. as suggested results, content Nrf2 well HO-1, i.e., downstream antioxidant proteins pertaining Nrf2, while decreasing BBB degradation tight junction proteins. To simulate condition hypoxia ischemia vitro, HBMEC cells received exposure deprivation (OGD). The treatment capable reducing barrier after vitro reperfusion (H/R). Furthermore, evidenced that could exhibit higher susceptibility H/R-induced ML385 application, inhibitor Nrf2. Besides, protection mediated disappeared application. sum up, revealed mentioned exert neuroprotective via pathway activation. Accordingly, play key role provide new pharmacology target DCA.

Language: Английский

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Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2846 - 2846

Published: March 5, 2022

Oxidative stress is a major component of cell damage and fat, as such, it occupies central position in the pathogenesis metabolic disease. Nuclear factor-erythroid-derived 2-related factor 2 (Nrf2), key transcription that coordinates expression genes encoding antioxidant detoxifying enzymes, regulated primarily by Kelch-like ECH-associated protein 1 (Keap1). However, involvement Keap1–Nrf2 pathway tissue organism homeostasis goes far beyond protection from cellular stress. In this review, we focus on evidence for Nrf2 dysfunction during development several metabolic/inflammatory disorders, including diabetes diabetic complications, obesity, inflammatory bowel disease, autoimmune diseases. We also review beneficial role current molecular agonists summarize their use ongoing clinical trials. conclude promising target regulation numerous diseases associated with oxidative inflammation. more studies are needed to explore safety implications before therapeutic practice.

Language: Английский

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Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

Antioxidants, Journal Year: 2022, Volume and Issue: 11(2), P. 301 - 301

Published: Jan. 31, 2022

Chronic kidney disease (CKD) can be considered as a clinical model for premature aging. However, non-invasive biomarkers to detect early damage and the onset of senescent phenotype are lacking. Most preclinical senescence studies in aging have been done very old mice. Furthermore, precise characterization over-time development age-related remain unclear. To address these limitations, activation cellular senescence-associated mechanisms their correlation with structural changes were investigated 3- 18-month-old C57BL6 Inflammatory cell infiltration was observed by 12 months, whereas tubular collagen accumulation occurred later. Early cellular-senescence-associated found 12-month-old mice, characterized DNA-damage-response (DDR), mainly cells; antioxidant NRF2 pathway; klotho downregulation. induction tubular-cell-cycle-arrest (CCA) overexpression renal senescent-associated secretory (SASP) components only In both inflammation oxidative stress (marked elevated lipid peroxidation inactivation) remained increased. These findings support hypothesis that prolonged DDR CCA, loss nephroprotective factors (klotho), dysfunctional redox regulatory (NRF2/antioxidant defense) drivers kidney-damage progression.

Language: Английский

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The crosstalk between Nrf2 and NF-κB pathways in coronary artery disease: Can it be regulated by SIRT6?

Life Sciences, Journal Year: 2023, Volume and Issue: 330, P. 122007 - 122007

Published: Aug. 5, 2023

Language: Английский

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Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway

Renal Failure, Journal Year: 2023, Volume and Issue: 45(1)

Published: March 20, 2023

Objectives: Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus. This study investigated mechanism triptolide (TP) in podocyte injury DN.Methods: DN mouse models were established by feeding with a high-fat diet and injecting streptozocin MPC5 induced high-glucose (HG), followed TP treatment. Fasting blood glucose renal function indicators, such as 24 h urine albumin (UAlb), serum creatinine (SCr), urea nitrogen (BUN), kidney/body weight ratio mice examined. H&E TUNEL staining performed for evaluating pathological changes apoptosis tissue. The markers, reactive oxygen species (ROS), oxidative stress (OS), inflammatory cytokines, nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway-related proteins, pyroptosis detected Western blotting corresponding kits. cell viability evaluated MTT Hoechst 33342/PI double-fluorescence staining. Nrf2 inhibitor ML385 was used to verify regulation on Nrf2.Results: improved histopathological mice, alleviated podocytes injury, reduced OS ROS activating Nrf2/heme oxygenase-1 (HO-1) pathway, weakened inhibiting nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome pathway. In vitro experiments further verified inhibition mediating Nrf2/HO-1 NLRP3 pathways. Inhibition reversed protective effect cells.Conclusions: Overall, via Nrf2/ROS/NLRP3 axis.

Language: Английский

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NIR-responsive molybdenum (Mo)-based nanoclusters enhance ROS scavenging for osteoarthritis therapy

Pharmacological Research, Journal Year: 2023, Volume and Issue: 192, P. 106768 - 106768

Published: April 13, 2023

Osteoarthritis (OA) is one of the most prevalent musculoskeletal disorders globally, and treating OA remains a significant challenge. Currently, pharmacological treatments primarily aim to alleviate symptoms associated with inflammation pain, no disease-modifying therapies are available delay development progression. Reactive oxygen species (ROS) play an essential role in progression, which promising target for curing OA. In this study, it was found that photothermal properties near-infrared (NIR) irradiation enhanced ROS scavenging activity molybdenum-based polyoxometalate (POM) nanoclusters. Because scavenging, NIR-responsive POM nanoclusters were developed as novel excellent nano-antioxidants protection. The results demonstrated exhibited outstanding antioxidant superexcellent anti-inflammatory effects, could effectively clinical mice, diminish inflammatory cytokines, reduce catabolic proteases, mitigate progression Meanwhile, local treatment had side effects on normal tissues. Thus, study pioneered application alleviating expected safety efficiency.

Language: Английский

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Ellagic acid ameliorates aging-induced renal oxidative damage through upregulating SIRT1 and NRF2

BMC Complementary Medicine and Therapies, Journal Year: 2023, Volume and Issue: 23(1)

Published: March 10, 2023

Abstract Background Aging is associated with impaired renal function and structural alterations. Oxidative stress plays a vital role in senescence damage. Sirtuin 1 (SIRT1) thought to protect cells from oxidative through nuclear factor erythroid 2-related 2 (NRF2). Ellagic acid (EA), natural antioxidant, has been demonstrated have renoprotective roles vitro vivo. This study investigated if SIRT1 NRF2 mediate the protective effects of EA aged kidneys. Methods Male Wistar rats were divided into three groups including young (4 months), old, old + (25 months). Young received solvent, while group was treated (30 mg/kg) by gavage for 30 days. Then, level stress, expression, kidney parameters, histopathological indices measured. Results Treatment significantly increased antioxidant enzymes reduced malondialdehyde concentration ( P < 0.01). Moreover, administration remarkably upregulated mRNA protein levels as well deacetylated 0.05). Additionally, improved scores Conclusions These findings suggest that ellagic exerts on kidneys activating signaling.

Language: Английский

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