Paeoniflorin alleviates ischemia/reperfusion induced acute kidney injury by inhibiting Slc7a11-mediated ferroptosis

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 116, P. 109754 - 109754

Published: Feb. 6, 2023

The pathophysiological mechanism of acute kidney injury (AKI) is complicated, and effective drugs are still lacking. Ferroptosis a newly discovered regulatory cell death mode characterized by the lethal accumulation iron reactive oxygen species-(ROS-)-dependent lipid hydroperoxides. In recent years, ferroptosis has been confirmed to be involved in progression AKI. Paeoniflorin (PF) traditional Chinese medicine that protective effects on variety diseases including However, which PF attenuates AKI unclear. We detected attenuated serum biochemical markers, histological damage, inflammation dose-dependent manner mouse model with bilateral renal artery ischemia-reperfusion (IR). Hypoxia-reoxygenation (HR)-induced was also inhibited human tubular epithelial cells (HK2). RNA sequence analysis revealed HK2 upregulating Slc7a11 glutathione pathway after HR treatment. failed further protect specific knockdown from under conditions. Consequently, these data indicated prevention requires dependence Slc7a11. This study provided scientific basis for clinical search prevent IR induced

Language: Английский

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Oxidative Stress, Reductive Stress and Antioxidants in Vascular Pathogenesis and Aging

Antioxidants, Journal Year: 2023, Volume and Issue: 12(5), P. 1126 - 1126

Published: May 19, 2023

This review is focused on the mechanisms that regulate health, disease and aging redox status, signal pathways counteract oxidative reductive stress, role of food components additives with antioxidant properties (curcumin, polyphenols, vitamins, carotenoids, flavonoids, etc.), hormones irisin melatonin in homeostasis animal human cells. The correlations between deviation from optimal conditions inflammation, allergic, autoimmune responses are discussed. Special attention given to vascular system, kidney, liver brain stress processes. hydrogen peroxide as an intracellular paracrine molecule also reviewed. cyanotoxins β-N-methylamino-l-alanine (BMAA), cylindrospermopsin, microcystins nodularins introduced potentially dangerous environment pro-oxidants.

Language: Английский

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Ferroptosis and endoplasmic reticulum stress in ischemic stroke

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(3), P. 611 - 618

Published: July 20, 2023

Abstract Ferroptosis is a form of non-apoptotic programmed cell death, and its mechanisms mainly involve the accumulation lipid peroxides, imbalance in amino acid antioxidant system, disordered iron metabolism. The primary organelle responsible for coordinating external challenges internal demands endoplasmic reticulum, progression inflammatory diseases can trigger reticulum stress. Evidence has suggested that ferroptosis may share pathways or interact with stress many plays role survival. occur after ischemic stroke. However, there are few reports on interactions This review summarized recent research relationships between stroke, aiming to provide reference developing treatments

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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Inhibition of ACSL4 ameliorates tubular ferroptotic cell death and protects against fibrotic kidney disease

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Sept. 5, 2023

Ferroptosis is a recently recognized form of regulated cell death, characterized by iron-dependent accumulation lipid peroxidation. Ample evidence has depicted that ferroptosis plays an essential role in the cause or consequence human diseases, including cancer, neurodegenerative disease and acute kidney injury. However, exact underlying mechanism fibrotic remain unknown. Acyl-CoA synthetase long-chain family member 4 (ACSL4) been demonstrated as component execution shaping composition. In this study, we aim to discuss potential ACSL4-mediated tubular epithelial cells (TECs) during renal fibrosis. The unbiased gene expression studies showed ACSL4 was tightly associated with decreased function progression To explore kidney, specific inhibitor rosiglitazone (ROSI) used disturb high TECs induced TGF-β, unilateral ureteral obstruction (UUO) fatty acid (FA)-modeled mice vivo, siRNA knockdown TGF-β-induced HK2 vitro. results inhibition effectively attenuated occurrence alleviated interstitial response. addition, various profibrotic cytokines all after ROSI-treated vivo Further investigation obviously attenuates fibrosis reducing proferroptotic precursors arachidonic acid- adrenic containing phosphatidylethanolamine (AA-PE AdA-PE). conclusion, these suggest for ferroptotic death development viable therapeutic approach preventing diseases.

Language: Английский

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