Regulating Nrf2-GPx4 axis by bicyclol can prevent ferroptosis in carbon tetrachloride-induced acute liver injury in mice

Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: Sept. 7, 2022

Hepatocellular death is a sensitive parameter for detecting acute liver injury (ALI) of toxic, viral, metabolic, and autoimmune origin. Ferroptosis has recently been implicated in carbon tetrachloride (CCl4)-induced ALI. However, the underpinning mechanism mechanistic basis remain elusive. In this study, bicyclol, proprietary hepatoprotectant China, ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) were administered CCl4-injured mice. A panel ferroptosis-related markers, including mitochondria morphology, reactive oxygen species production, protein adducts response to lipid peroxidation, key modulators ferroptotic process, was determined vivo. Erastin-treated L-O2 hepatocytes transfected with glutathione peroxidase 4 (GPx4) or nuclear factor erythroid 2-related 2 (Nrf2) siRNA delineate pathway bicyclol against ferroptosis vitro. As result, CCl4 led iron accumulation, excessive enhanced characteristic morphological changes mitochondria, along decrease GPx4 xCT levels ALI mice liver, all which generally observed ferroptosis. The use Fer-1 further corroborated that responsible damage. Bicyclol exerted its hepatoprotection by preventing aforesaid process. Furthermore, alleviated erastin-induced cellular inviability, destruction, peroxidation Knockdown diminished these protective activities perturbations associated hepatocytes. Additionally, Nrf2 silencing drastically reduced levels, impeded medicinal effects bicyclol. summary, positively regulating Nrf2-GPx4 axis can prevent CCl4-induced

Language: Английский

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Ginsenoside Rd Inhibited Ferroptosis to Alleviate CCl₄-Induced Acute Liver Injury in Mice via cGAS/STING Pathway

The American Journal of Chinese Medicine, Journal Year: 2022, Volume and Issue: 51(01), P. 91 - 105

Published: Nov. 28, 2022

Carbon tetrachloride (CCl4)-induced lipid peroxidation associated with hepatic oxidative stress and cell death is an important mechanism of acute liver injury (ALI). Ginsenoside Rd considered active ingredient ginseng. Evidence suggests that ginsenoside may improve ischaemic stroke, nerve damage, cancer other diseases involving apoptosis, inflammation, stress, mitochondrial autophagy. However, the effects on CCl4-induced ALI its underlying mechanisms are still unclear. In this study, 0.25% CCl4 was injected intraperitoneally in mice to establish a model. treatment group, (10, 20[Formula: see text]mg/kg) doses were 1[Formula: text]h before 23[Formula: after administration. Ferroptosis inducer imidazole ketone erastin (IKE) 4[Formula: administration explore mechanism. The blood collected 24[Formula: investigate effect ALI. Our results showed inhibited mice. also downregulated serum iron, 4-hydroxynonenal, 8-hydroxy-2 deoxyguanosine levels. Furthermore, it upregulated glutathione peroxidase 4 addition, expression cGAS STING. Subsequently, ferroptosis significantly reversed hepatoprotective influence regard indicators mentioned above. study confirmed ameliorated mice, which related reduction ferroptosis. Simultaneously, Rd-mediated inhibition cGAS/STING pathway contributed antiferroptosis effect. conclusion, our suggested via pathway, thereby protecting from These be used as potential intervention against

Language: Английский

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Manipulating the antioxidative capacity of melanin-like nanoparticles by involving condensation polymerization

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(5), P. 1520 - 1528

Published: April 17, 2023

Language: Английский

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Matrine disrupts Nrf2/GPX4 antioxidant system and promotes hepatocyte ferroptosis

Chemico-Biological Interactions, Journal Year: 2023, Volume and Issue: 384, P. 110713 - 110713

Published: Sept. 15, 2023

Language: Английский

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Baicalein alleviates cisplatin-induced acute kidney injury by inhibiting ALOX12-dependent ferroptosis

Phytomedicine, Journal Year: 2024, Volume and Issue: 130, P. 155757 - 155757

Published: May 17, 2024

Language: Английский

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Molecular Mechanisms of Ferroptosis and Its Roles in Hematologic Malignancies

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Oct. 27, 2021

Cell death is essential for the normal metabolism of human organisms. Ferroptosis a unique regulated cell (RCD) mode characterized by excess accumulation iron-dependent lipid peroxide and reactive oxygen species (ROS) compared with other well-known programmed modes. It has been currently recognized that ferroptosis plays rather important role in occurrence, development, treatment traumatic brain injury, stroke, acute kidney liver damage, ischemia–reperfusion tumor, etc. Of note, may be explained expression various molecules signaling components, among which iron, lipid, amino acid are key regulatory mechanisms ferroptosis. Meanwhile, tumor cells hematological malignancies, such as leukemia, lymphoma, multiple myeloma (MM), identified to sensitive Targeting potential factors pathway promote or inhibit disease progression these malignancies. In this review, systematic summary was conducted on molecular current relationships MM. expected provide novel therapeutic approaches targets

Language: Английский

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A small molecule targeting ALOX12-ACC1 ameliorates nonalcoholic steatohepatitis in mice and macaques

Science Translational Medicine, Journal Year: 2021, Volume and Issue: 13(624)

Published: Dec. 15, 2021

IMA-1 targets the ALOX12-ACC1 interaction to both prevent and treat NASH without inducing hyperlipidemia.

Language: Английский

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Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

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

Published: July 12, 2022

Low back pain is a major cause of disability worldwide that declines the quality life; it poses substantial economic burden for patient and society. Intervertebral disc (IVD) degeneration (IDD) main low pain, also pathological basis several spinal degenerative diseases, such as intervertebral herniation stenosis. The current clinical drug treatment IDD focuses on symptoms not their pathogenesis, which results in frequent recurrence gradual aggravation. Moreover, side effects associated with long-term use these drugs further limit use. mechanism complex, oxidative stress inflammation play an important role promoting IDD. They induce destruction extracellular matrix IVD reduce number living cells functional cells, thereby destroying function occurrence development Phytochemicals from fruits, vegetables, grains, other herbs protective they have anti-inflammatory antioxidant properties. This article reviews phytochemicals regulatory different molecular pathways related to pathogenesis therapeutic limitations future prospects been reviewed. are promising candidates research treatment.

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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Nootkatone Supplementation Ameliorates Carbon Tetrachloride-Induced Acute Liver Injury via the Inhibition of Oxidative Stress, NF-κB Pathways, and the Activation of Nrf2/HO-1 Pathway

Antioxidants, Journal Year: 2023, Volume and Issue: 12(1), P. 194 - 194

Published: Jan. 13, 2023

Acute liver injury is a type of diseases, and it has raised concerns worldwide due to the lack effective therapies. The aim this study investigate protective effects nootkatone (NOOT) on carbon tetrachloride (CCl4)-caused acute in mice. Mice were randomly divided into control, CCl4 model, NOOT, NOOT (5, 10, 20 mg/kg/day) plus groups, respectively. groups orally administrated with at 5, mg/kg/days for seven days prior 0.3% injection 10 mL/kg body weight, Our results showed that supplementation significantly ameliorated CCl4-induced increases serum AST ALT levels, hepatocyte necrosis, inflammatory response, oxidative stress, caspases-9 -3 activities livers Moreover, upregulated expression Nrf2 HO-1 mRNAs but downregulated NF-κB levels IL-1β, IL-6, TNF-α proteins tissues, compared those model group. In conclusion, first time, our reveal could offer against CCl4-caused stress response via opposite regulation Nrf2/HO-1 pathway pathway.

Language: Английский

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