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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Butylated Hydroxytoluene (BHT) Protects SH-SY5Y Neuroblastoma Cells from Ferroptotic Cell Death: Insights from In Vitro and In Vivo Studies

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 242 - 242

Published: Feb. 17, 2024

Ferroptosis is a special kind of programmed cell death that has been implicated in the pathogenesis large number human diseases. It involves dysregulated intracellular iron metabolism and uncontrolled lipid peroxidation, which together initiate ferroptotic signalling pathways leading to cellular suicide. Pharmacological interference with signal transduction may prevent death, thus patients suffering from ferroptosis-related diseases benefit such treatment. Butylated hydroxytoluene (BHT) an effective anti-oxidant frequently used oil chemistry cosmetics free-radical-mediated peroxidation. Since it functions as radical scavenger, previously reported interfere signalling. Here, we show BHT prevents RSL3- ML162-induced cultured neuroblastoma cells (SH-SY5Y) dose-dependent manner. RSL3-induced oxidation membrane lipids normalises inhibition catalytic activity glutathione peroxidase 4. The systemic application rat Alzheimer’s disease model prevented upregulation expression genes. Taken together, these data indicate interferes animal model.

Language: Английский

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Ferroptosis as a potential therapeutic target for age-related macular degeneration

Drug Discovery Today, Journal Year: 2024, Volume and Issue: 29(4), P. 103920 - 103920

Published: Feb. 17, 2024

Language: Английский

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TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway

Phytomedicine, Journal Year: 2024, Volume and Issue: 129, P. 155597 - 155597

Published: April 21, 2024

Language: Английский

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Hinokitiol ameliorates MASH in mice by therapeutic targeting of hepatic Nrf2 and inhibiting hepatocyte ferroptosis

Phytomedicine, Journal Year: 2025, Volume and Issue: 139, P. 156472 - 156472

Published: Feb. 5, 2025

Language: Английский

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Carbon Dot Nanozymes with Ferrous Ion‐Chelating and Antioxidative Activity Inhibiting Ferroptosis to Alleviate Renal Ischemia‐Reperfusion Injury

Small, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Renal ischemia-reperfusion (I/R) significantly contributes to acute kidney injury (AKI), causing substantial oxidative stress and metabolic disruptions. Ferroptosis, a Fe2+-dependent form of regulated cell death characterized by lipid peroxide accumulation, is the predominant cause renal I/R (RIRI). Here, carbon dot (C-dot) nanozymes that inhibit ferroptosis regulating Fe2⁺ levels scavenging reactive oxygen species, offering potential treatment for RIRI are reported. C-dots chelate via surface carbonyl, hydroxyl, carboxyl groups reduce free levels, suppress Fenton reaction, limit hydroxyl radical generation. Additionally, scavenge superoxide anions radicals restore redox balance. By targeting kidneys, effectively iron overload peroxidation prevent ferroptotic in male mice model. RNA sequencing (RNA-seq) analysis further confirms crucial roles mitigating stress, preserving homeostasis, downregulating acyl-CoA synthetase long-chain family member 4 (ACSL4) after I/R. This work emphasizes perfect alignment between multifunctional conditions required inhibiting offers an innovative strategy treat effectively.

Language: Английский

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The Regulation of Trace Metal Elements in Cancer Ferroptosis

Advanced Biology, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract Ferroptosis, as novel type of regulated cell death that has garnered widespread attention over the past decade, witnessed continuous discovery an increasing number regulatory mechanisms. Trace metal elements play a multifaceted and crucial role in oncology. Interestingly, it been increasingly evident these elements, such copper, are involved regulation iron accumulation, lipid peroxidation antiferroptotic systems, suggesting existence “nonferrous” mechanisms ferroptosis. In this review, comprehensive overview composition mechanism ferroptosis is provided. The interaction between copper metabolism (including cuproptosis) cancer, well roles other trace (such zinc, manganese, cobalt, molybdenum) specifically focused. Furthermore, applications nanomaterials based on metals cancer therapy also reviewed potential strategies for co‐targeting cuproptosis explored. Nevertheless, light intricate ambiguous nature interactions, ongoing research essential to further elucidate ferroptosis, thereby facilitating development therapeutic targets approaches treatment.

Language: Английский

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Melatonin and ferroptosis: Mechanisms and therapeutic implications

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 218, P. 115909 - 115909

Published: Nov. 4, 2023

Language: Английский

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Design, synthesis, and evaluation of formylpiperazine analogs of Ferrostatin-1 as novel improved ferroptosis inhibitors

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 105, P. 117716 - 117716

Published: April 9, 2024

Language: Английский

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Ferroptosis as an emerging target in sickle cell disease

Current Research in Toxicology, Journal Year: 2024, Volume and Issue: 7, P. 100181 - 100181

Published: Jan. 1, 2024

Sickle cell disease (SCD) is an inherited hemoglobin disorder marked by red blood sickling, resulting in severe anemia, painful episodes, extensive organ damage, and shortened life expectancy. In SCD, increased iron levels can trigger ferroptosis, a specific type of death characterized reactive oxygen species (ROS) lipid peroxide accumulation, leading to damage impairments. The intricate interplay between iron, inflammation, oxidative stress SCD underscores the necessity thoroughly understanding these processes for development innovative therapeutic strategies. This review highlights importance balancing complex interactions among various factors exploitation knowledge developing novel therapeutics this devastating disease.

Language: Английский

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