Naringenin Inhibits Ferroptosis in Renal Tubular Epithelial Cells of Diabetic Nephropathy Through SIRT1/FOXO3a Signaling Pathway

Drug Development Research, Journal Year: 2025, Volume and Issue: 86(1)

Published: Jan. 12, 2025

ABSTRACT Naringenin has the potential to regulate ferroptosis and mitigate renal damage in diabetic nephropathy (DN). However, it remains unclear whether naringenin's effects DN are linked its ability ferroptosis. This study investigated anti‐ferroptosis properties of naringenin high glucose (HG)‐induced tubular epithelial cell models. HK‐2 cells were cultured HG medium establish model. treated with different doses explore effect naringenin. The CCK‐8 results show that 50 μM ~ 200 do not affect viability HG‐induced increase a dose‐dependent manner treatment. Additionally, increased levels IL‐10 while decreasing IL‐1β, TNF‐α, IL‐6, ROS cells. also reduced Fe 2+ , oxidized lipid ROS, MDA, 4‐HNE, ACSL4, TFR1 cells, increasing non‐oxidized SOD, GSH‐Px, SLC7A11, GPX4. Meanwhile, restored MMP, ATP MPTP opening, OCR Furthermore, reversed decreased expression SIRT1, p‐FOXO3a, Nrf2 Nuclear caused by HG. SIRT1 inhibitor EX527 ML385 attenuated on demonstrating stronger reversal than ML385. These suggest inhibits mainly through SIRT1/FOXO3a signaling pathway. finding further enhanced our understanding mechanism behind protective DN.

Language: Английский

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Emerging significance and therapeutic targets of ferroptosis: a potential avenue for human kidney diseases

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(9)

Published: Sept. 22, 2023

Abstract Kidney diseases remain one of the leading causes human death and have placed a heavy burden on medical system. Regulated cell contributes to pathology plethora renal diseases. Recently, with in-depth studies into kidney death, new iron-dependent modality, known as ferroptosis, has been identified attracted considerable attention among researchers in pathogenesis therapeutics treat them. The majority suggest that ferroptosis plays an important role pathologies multiple diseases, such acute injury (AKI), chronic disease, carcinoma. In this review, we summarize recently regulatory molecular mechanisms discuss pathways action various describe protective effect inhibitors against especially AKI. By summarizing prominent roles different progress made studying provide directions strategies for future research summary, ferroptotic factors are potential targets therapeutic intervention alleviate targeting them may lead treatments patients

Language: Английский

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Ferroptosis and cuproptposis in kidney Diseases: dysfunction of cell metabolism

APOPTOSIS, Journal Year: 2023, Volume and Issue: 29(3-4), P. 289 - 302

Published: Dec. 14, 2023

Metal ions play an important role in living organisms and are involved essential physiological activities. However, the overload state of can cause excess free radicals, cell damage, even death. Ferroptosis cuproptosis specific forms death that distinct from apoptosis, necroptosis, other regulated These unique modalities death, dependent on iron copper, by multiple cellular metabolic pathways, including steady-state metal redox treatment mitochondrial activity lipid, amino acid glucose metabolism, various signaling pathways associated with disease. Although mechanisms ferroptosis not yet fully understood, there is no doubt ion plays a crucial act these metal-dependent deaths. In this review, we discussed core roles cuproptosis, association between metabolism imbalance extract diseases caused current modalities.

Language: Английский

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Role of oxidative stress‐induced ferroptosis in cancer therapy

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(10)

Published: May 1, 2024

Abstract Ferroptosis is a distinct mode of cell death, distinguishing itself from typical apoptosis by its reliance on the accumulation iron ions and lipid peroxides. Cells manifest an imbalance between oxidative stress antioxidant equilibrium during certain pathological contexts, such as tumours, resulting in stress. Notably, recent investigations propose that heightened intracellular reactive oxygen species (ROS) due to can heighten cellular susceptibility ferroptosis inducers or expedite onset ferroptosis. Consequently, comprehending role ROS initiation has significance elucidating disorders related Moreover, exhaustive exploration into mechanism control might offer novel targets for addressing specific tumour types. Within this context, our review delves fundamental pathways molecular foundation Four classical ferroptotic are well characterized, namely, glutathione peroxidase 4‐centred pathway, nuclear factor erythroid 2‐related 2 mitochondrial mTOR‐dependent autophagy pathway. Furthermore, we seek elucidate regulatory contributions enacted ROS. Additionally, provide overview targeted medications targeting four implicated their potential clinical applications. Here, ferroptosis, discuss opportunities use new strategy cancer therapy point out current challenges persisting within domain ROS‐regulated anticancer drug research development.

Language: Английский

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Tetramethylpyrazine attenuates renal tubular epithelial cell ferroptosis in contrast-induced nephropathy by inhibiting transferrin receptor and intracellular reactive oxygen species

Clinical Science, Journal Year: 2024, Volume and Issue: 138(5), P. 235 - 249

Published: Feb. 15, 2024

Abstract Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury (AKI). Recently, ferroptosis was reported to be crucial for AKI pathogenesis. Our previous studies indicated antioxidant tetramethylpyrazine (TMP) prevent CIN in vivo. However, whether involved TMP nephroprotective mechanism against unclear. In the present study, we investigated role renal tubular epithelial cell reno-protective effect and molecular mechanisms by which regulates ferroptosis. Classical contrast-medium, Iohexol, used construct models rats HK-2 cells. Results showed that accompanied both vivo vitro, including typical features ferroptosis, Fe2+ accumulation, lipid peroxidation decreased glutathione peroxidase 4 (GPX4). Ferroptosis inhibition classic inhibitors Fer-1 DFO promoted viability reduced intracellular ROS production. Additionally, significantly inhibited dysfunction, biomarkers, prevented production, accumulation increased GPX4 expression. Expressions various proteins associated with iron ion metabolism, transferrin receptor (TFRC), divalent metal transporter 1, iron-responsive element binding protein 2, ferritin heavy chain ferroportin heat shock factor were examined using mechanistic analyses. Among these, TFRC changes most significant after pretreatment. siRNA knockdown plasmid overexpression essential alleviate reduce LDH release, ROS. findings provide insights about potential treating

Language: Английский

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Baicalein ameliorates polymyxin B-induced acute renal injury by inhibiting ferroptosis via regulation of SIRT1/p53 acetylation

Chemico-Biological Interactions, Journal Year: 2023, Volume and Issue: 382, P. 110607 - 110607

Published: June 23, 2023

Language: Английский

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Morroniside alleviates cisplatin-induced renal injury and gut dysbiosis via the gut–kidney axis and ferroptosis

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 153, P. 114430 - 114430

Published: March 17, 2025

Language: Английский

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Ultrasound-responsive Bi2MoO6-MXene heterojunction as ferroptosis inducers for stimulating immunogenic cell death against ovarian cancer

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 11, 2024

Abstract Background Ovarian cancer (OC) has the highest fatality rate among all gynecological malignancies, necessitating exploration of novel, efficient, and low-toxicity therapeutic strategies. Ferroptosis is a type programmed cell death induced by iron-dependent lipid peroxidation can potentially activate antitumor immunity. Developing highly effective ferroptosis inducers may improve OC prognosis. Results In this study, we developed an ultrasonically controllable two-dimensional (2D) piezoelectric nanoagonist (Bi 2 MoO 6 -MXene) to induce ferroptosis. A Schottky heterojunction between Bi (BMO) MXene reduced bandgap width 0.44 eV, increased carrier-separation efficiency, decreased recombination electron–hole pairs under ultrasound stimulation. Therefore, reactive oxygen species yield was enhanced. Under spatiotemporal excitation, BMO-MXene effectively inhibited proliferation more than 90%, peroxidation, mitochondrial-membrane potential, inactivated glutathione peroxidase cystathionine transporter protein system, thereby causing in tumor cells. cells further activated immunogenic death, facilitating dendritic maturation stimulating Conclusion We have succeeded developing potent inducer (BMO-MXene), capable inhibiting progression through sonodynamic-ferroptosis-immunogenic pathway. Graphical

Language: Английский

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A new strategy for the treatment of intracerebral hemorrhage: Ferroptosis

Experimental Neurology, Journal Year: 2024, Volume and Issue: 382, P. 114961 - 114961

Published: Sept. 15, 2024

Language: Английский

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The role of ferroptosis in acute kidney injury: mechanisms and potential therapeutic targets

Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: June 28, 2024

Language: Английский

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