Life Sciences, Journal Year: 2025, Volume and Issue: 371, P. 123609 - 123609
Published: April 5, 2025
Language: Английский
Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)
Published: Oct. 16, 2023
Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.
Language: Английский
Citations
62
International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 276, P. 133792 - 133792
Published: July 9, 2024
Language: Английский
Citations
8
Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)
Published: Jan. 1, 2025
ABSTRACT The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which primarily attributed interaction with iron in mitochondria, leading lipid peroxidation and myocardial ferroptosis. This study aimed investigate the role gut microbiota‐derived metabolite, indole‐3‐lactic acid (ILA), mitigating DOX‐induced cardiotoxicity (DIC). Cardiac function, pathological changes, ferroptosis were assessed vivo. cardioprotective effects mechanisms ILA explored using multi‐omics approaches, including single‐nucleus RNA sequencing (snRNA‐seq) bulk RNA‐seq, further validated Nrf2 knockout mice. findings revealed that DOX treatment disrupted microbiota, significantly reducing levels tryptophan metabolite ILA. In DIC models, supplementation markedly improved cardiac reduced collagen deposition, mitigated atrophy. snRNA‐seq analyses indicated played a crucial Experimental data demonstrated decreased both mice DOX‐treated H9C2 cells, evidenced by restoration GPX4 SLC7A11 reduction ACSL4. Mechanistically, functions as ligand for aryl hydrocarbon receptor (AhR), upregulation expression. protective against abolished silencing AhR. Moreover, beneficial on eliminated Nrf2‐deficient conclusion, exerts therapeutic inhibiting through activation AhR/Nrf2 signalling pathway. Identifying microbial could offer viable strategies DIC.
Language: Английский
Citations
1
Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14
Published: April 12, 2023
Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii , shows unique efficacy reviving Yang resuscitation, which widely used clinics. As main cardiotonic component mesaconine proven various cardiomyopathy models. Here, we aimed to define previously unrevealed cardioprotective mechanism mesaconine-mediated restoration obstructive mitophagy. The functional implications were evaluated doxorubicin (DOX)-induced heart failure DOX-treated mice showed characteristic dysfunction, ectopic myocardial disorder, impaired cardiomyocytes, could be remarkably reversed by mesaconine. effect was primarily attributed its ability promote evidenced elevated expression PINK1, key mediator induction. Silencing PINK1 or deactivating completely abolish protective effects Together, our findings suggest that appear dependent on activation PINK1-induced may constitute promising therapeutic agent treatment failure.
Language: Английский
Citations
20
Environmental Research, Journal Year: 2023, Volume and Issue: 234, P. 116504 - 116504
Published: June 24, 2023
Language: Английский
Citations
20
Toxicology, Journal Year: 2023, Volume and Issue: 494, P. 153597 - 153597
Published: July 25, 2023
Language: Английский
Citations
19
Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 326, P. 117941 - 117941
Published: Feb. 20, 2024
Language: Английский
Citations
8
Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(3), P. 359 - 359
Published: March 10, 2024
Andaliman (Zanthoxylum acanthopodium DC.) fruit is a spice plant widely used in North Sumatra. The chemical content the has cardioprotective effect, with antioxidant properties that inhibit oxidative stress and free radicals. SOD (superoxide dismutase), BNP (Brain Natriuretic Peptide), cTnT (troponin T) are measured as markers of heart damage, histopathology to see damage. Quercetin administration was comparison. hydroalcoholic extract's phytochemical elements were analyzed using LC-HRMS GC-MS. findings showed hydroalcohol extract fruits affected blood levels SOD, BNP, doxorubicin-induced rats. increased, decreased; 300 mg/kg BW group not significantly different from 50 quercetin group. also 150 groups different, both better than EAF can repair damage rat tissue caused by doxorubicin. effects anti-free radical activity due its potential be developed.
Language: Английский
Citations
7
Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(8), P. 4134 - 4147
Published: April 23, 2024
Doxorubicin (DOX) is a broad-spectrum antibiotic with potent anti-cancer activity. Nevertheless, despite having effective anti-neoplasm activity, its use has been clinically restricted due to life-threatening side effects, such as cardiotoxicity. It evident that betaine anti-oxidant, and anti-inflammatory activity several beneficial decreasing the amyloid-β generation, reducing obesity, improving steatosis fibrosis, activating AMP-activated protein kinase (AMPK). However, whether could mitigate DOX-induced cardiomyopathy still unexplored. Cardiomyopathy was induced in male Sprague Dawley rats using DOX (4 mg/kg dose cumulative of 20 mg/kg, i.p.). Further, (200 400 mg/kg) co-treated through oral gavage for 28 days. After completion study, biochemical, oxidative stress parameters, histopathology, western blotting, qRT-PCR were performed. Betaine treatment significantly reduced CK-MB, LDH, SGOT, triglyceride levels, which are associated increased also mitigated by intervention SOD, catalase, MDA, nitrite levels restored. The histopathological investigation confirmed cardioprotective effect against tissue injury reversed. molecular analysis revealed suppressed expression phospho-p53, phospho-p38 MAPK, NF-kB p65, PINK 1 an upregulation AMPK downregulation Nrf2 expression. Interestingly, experiments show alleviates increase inflammatory (TNF-α, NLRP3, IL-6) fibrosis (TGF-β Acta2) related gene expression, halting cardiac injury. improves mRNA Nrf2, thus modulating antioxidant proteins preventing damage. Here, we provide first evidence prevents inhibiting stress, inflammation, regulating AMPK/Nrf2/TGF-β We believe can be utilized potential novel therapeutic strategy
Language: Английский
Citations
7
Cardiovascular Diagnosis and Therapy, Journal Year: 2024, Volume and Issue: 14(1), P. 84 - 100
Published: Feb. 1, 2024
Background: Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)-mediated reactive oxygen species (ROS) has been reported to induce cardiomyocyte apoptosis, but its effect on pyroptosis of cardiomyocytes rarely reported. This paper aimed explore the effects NOX4-mediated ROS production doxorubicin (DOX)-induced myocardial injury and through nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. Methods: HL-1 cells were treated with DOX or mice (30 divided into five groups six mice/group) underwent intraperitoneal injection (5 mg/kg, once a week, times) injury, followed by assessment NOX4 NLRP3 expression in cell supernatant tissues. In cells, proliferation was tested MTT assay activity probes. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, glutathione (GSH) evaluated kits. proteins assessed western blotting. Subsequently, altered determine pyroptosis. animal models utilized evaluate changes cardiac function using an echocardiographic system, these parameters measured including left ventricular ejection fraction (LVEF), fractional shortening (LVFS), end-diastolic diameter (LVEDD). Furthermore, content markers determined mice. Results: treatment led pyroptosis, as evidenced weakened LVEF, LVFS, (P<0.05), elevated LVEDD, ROS, MDA increased decreased SOD GSH (P<0.05). Additionally, highly-expressed (P<0.05) DOX-induced overexpression intensified levels aggravate which reversed scavenger N-acetyl-cysteine. it revealed that combination short hairpin RNA (sh)-NOX4 overexpressed (oe)-NLRP3 cardioprotective sh-NOX4 tissue vitro vivo. No died during experiments, only two ruled out due weight loss greater than 20%. Conclusions: activated inflammasome, thereby aggravating
Language: Английский
Citations
6