Exposure to 6-PPD quinone causes ferroptosis activation associated with induction of reproductive toxicity in Caenorhabditis elegans

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 471, P. 134356 - 134356

Published: April 19, 2024

Language: Английский

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Chronic arsenic exposure-provoked biotoxicity involved in liver-microbiota-gut axis disruption in chickens based on multi-omics technologies

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Arsenic has been ranked as the most hazardous substance by U.S. Agency for Toxic Substances and Disease Registry. Environmental arsenic exposure-evoked health risks have become a vital public concern worldwide owing to widespread existence of arsenic. Multi-omics is revolutionary technique data analysis providing an integrated view bioinformation comprehensively systematically understanding elaborate mechanism diseases. This study aimed at uncovering potential contribution liver-microbiota-gut axis in chronic inorganic exposure-triggered biotoxicity chickens based on multi-omics technologies. Forty Hy-Line W-80 laying hens were chronically exposed sodium arsenite with dose-dependent manner (administered drinking water containing 10, 20, or 30 mg/L arsenic, respectively) 42 d, followed transcriptomics, serum non-targeted metabolome, 16S ribosomal RNA gene sequencing accordingly. intervention induced serious chicken liver dysfunction, especially severe fibrosis, simultaneously altered ileal microbiota populations, impaired intestinal barrier, further drove enterogenous lipopolysaccharides translocation via portal vein circulation aggravating damage. Furtherly, injured disturbed bile acids (BAs) homoeostasis through strongly up-regulating BAs synthesis key rate-limiting enzyme CYP7A1, inducing excessive total accumulation, accompanied massive primary BA—chenodeoxycholic acid. Moreover, concentrations secondary BAs—ursodeoxycholic acid lithocholic markedly repressed, which might involve repressed dehydroxylation Ruminococcaceae Lachnospiraceae families. Abnormal metabolism turn promoted injury, ultimately perpetuating pernicious circle chickens. Notably, obvious depletion abundance four profitable microbiota, Christensenellaceae, Ruminococcaceae, Muribaculaceae, Faecalibacterium, correlated tightly this hepato-intestinal process Our demonstrates that exposure evokes disruption establishes scientific basis evaluating risk environmental pollutant

Language: Английский

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New insights into zinc alleviating renal toxicity of arsenic-exposed carp (Cyprinus carpio) through YAP-TFR/ROS signaling pathway

Pesticide Biochemistry and Physiology, Journal Year: 2024, Volume and Issue: 205, P. 106153 - 106153

Published: Sept. 25, 2024

Language: Английский

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Salidroside ameliorates acetaminophen-induced acute liver injury through the inhibition of endoplasmic reticulum stress-mediated ferroptosis by activating the AMPK/SIRT1 pathway

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 262, P. 115331 - 115331

Published: Aug. 7, 2023

Acetaminophen (APAP) overdose has long been considered a major cause of drug-induced liver injury. Ferroptosis is type programmed cell death mediated by iron-dependent lipid peroxidation. Endoplasmic reticulum (ER) stress systemic response triggered the accumulation unfolded or misfolded proteins in ER. and ER have proven to contribute progression APAP-induced acute injury (ALI). It was reported that salidroside protects against ALI, but potential mechanism remain unknown. In this study, male C57BL/6 J mice were intraperitoneally (i.p.) injected APAP (500 mg/kg) induce an ALI model. Salidroside i.p. at dose 100 mg/kg 2 h prior administration. Mice sacrificed 12 after injection serum obtained for histological biochemistry analysis. AML12 cells used vitro assays. The results indicated mitigated glutathione degradation via inhibiting cation transport regulator homolog 1 (CHAC1) attenuate ferroptosis, simultaneously suppressing PERK-eIF2α-ATF4 axis-mediated stress, thus alleviating ALI. However, PERK activator CCT020312 overexpression ATF4 inhibited protective function on CHAC1-mediated ferroptosis. Besides this, activation AMPK/SIRT1 signaling pathway demonstrated effect Interestingly, selective inhibition SIRT1 ameliorated effects Overall, plays significant part mitigation activating inhibit stress-mediated ferroptosis ATF4-CHAC1 axis.

Language: Английский

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The Importance and Essentiality of Natural and Synthetic Chelators in Medicine: Increased Prospects for the Effective Treatment of Iron Overload and Iron Deficiency

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4654 - 4654

Published: April 25, 2024

The supply and control of iron is essential for all cells vital many physiological processes. All functions activities are expressed in conjunction with iron-binding molecules. For example, natural chelators such as transferrin chelator–iron complexes haem play major roles metabolism human physiology. Similarly, the mainstay treatments most common diseases metabolism, namely deficiency anaemia overload, involve iron–chelator iron-chelating drugs deferiprone (L1), deferoxamine (DF) deferasirox. Endogenous citric acid glutathione exogenous ascorbic also important homeostasis. Recent advances treatment effective ferric tri-maltol complex (feraccru or accrufer) transfusional overload using L1 L1/DF combinations have decreased associated mortality morbidity improved quality life millions patients. Many other chelating ciclopirox, dexrazoxane EDTA used daily by patients diseases. their metabolites iron-chelation capacity hydroxyurea, tetracyclines, anthracyclines aspirin, well dietary molecules gallic acid, caffeic quercetin, ellagic maltol phytochelators, known to interact affect related Different interactions observed presence essential, xenobiotic, diagnostic theranostic metal ions competing iron. Clinical trials Parkinson’s, Alzheimer’s neurodegenerative diseases, HIV infections, cancer, diabetic nephropathy inflammation, highlight importance chelation therapy clinical conditions. proposed use modulating ferroptosis signifies a new era design therapeutic strategies introduction artificial intelligence guidance optimal outcomes personalised medicine expected increase further impact medicine, survival metabolic disorders

Language: Английский

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Nuclear receptor coactive 4-mediated ferritinophagy: a key role of heavy metals toxicity

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Language: Английский

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Quercetin alleviates LPS/iE-DAP-induced liver injury by suppressing ferroptosis via regulating ferritinophagy and intracellular iron efflux

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103557 - 103557

Published: Feb. 18, 2025

Ruminal dysbiosis-induced liver injury is prevalent in dairy cows, yet its underlying mechanisms remain incompletely understood. Ferroptosis, a newly identified form of programmed cell death distinct from apoptosis and necrosis, has been implicated various diseases by emerging studies. In the present study, lipopolysaccharide (LPS) γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) were employed to establish vitro vivo models using bovine hepatocytes mice, respectively. It was observed that noncytotoxic iE-DAP alone did not influence lipid peroxidation or GPX4, but exacerbated LPS-induced ferroptosis hepatocyte injury. Notably, co-treatment with LPS (LPS/iE-DAP)-induced mitigated intervention inhibitor ferrostatin-1 (Fer-1). Mechanistically, activated IL-6/STAT3 signaling pathway found mediate LPS/iE-DAP-induced ferroptosis. Suppression IL-6/STAT3, either through IL6 STAT3 knockdown pharmacological intervention, reduced Fe2+ accumulation alleviated ferroptotic death. Further investigations enhanced ferritinophagy impaired iron export. Either disrupting knocking down NCOA4 restoring export via HAMP relieved intracellular overload inhibited Specifically, LPS/iE-DAP treatment increased interaction between hepcidin ferroportin, promoting ferroportin ubiquitination degradation, thereby blocking efflux. Furthermore, we provided several evidence prove quercetin pretreatment decreasing hepatic targeting vivo, effects reversed addition recombinant IL-6. Based on these findings, concluded triggering regulating IL-6/STAT3/ferritinophagy-dependent release IL-6/STAT3/hepcidin/ferroportin-dependent export, while could alleviate this inhibiting pathway. This study provides novel insights into whereby ruminal dysbiosis induces presents prospective solution for

Language: Английский

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Downregulation of the (pro)renin receptor alleviates ferroptosis-associated cardiac pathological changes via the NCOA 4-mediated ferritinophagy pathway in diabetic cardiomyopathy

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 138, P. 112605 - 112605

Published: July 3, 2024

Language: Английский

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Salvianolic acid A attenuates arsenic-induced ferroptosis and kidney injury via HIF-2α/DUOX1/GPX4 and iron homeostasis

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 907, P. 168073 - 168073

Published: Oct. 23, 2023

Language: Английский

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Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood–testis barrier remodeling

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 22, 2024

Abstract This study aimed to investigate the effects of eugenol treatment on reproductive parameters in acrylamide (ACR)-intoxicated rats. The evaluated alterations relative testes and epididymides weights, sperm quality, serum hormonal status, seminal plasma amino acids, testicular cell energy phospholipids content, oxidative nitrosative stress parameters, adenosine monophosphate-activated protein kinase/ phosphoinositide 3-kinase/phosphor-protein kinase B/mammalian target rapamycin (AMPK/PI3K/p-AKT/mTOR) signaling pathway, blood–testis barrier (BTB) remodeling markers, autophagy apoptotic as well histopathological tissues. results revealed that demonstrated a significant improvement quality with increased concentration, progressive motility live sperm, reduction abnormal compared ACR-intoxicated group. Furthermore, administration levels acids dose-dependent manner. In addition, dose-dependently improved oxidative/nitrosative biomarkers by increasing oxidized reduced glutathione reducing malondialdehyde nitric oxide contents ACRgroup. However, at high dose restored expression AMPK, PI3K, mTOR genes, comparable control group, while significantly p-AKT content conclusion, obtained findings suggest potential therapeutic agent mitigating ACR-induced detrimental male system via amelioration ROS-mediated autophagy, apoptosis, AMPK/p-AKT/mTOR pathways BTB remodeling.

Language: Английский

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