Heavy metals: toxicity and human health effects

Archives of Toxicology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 20, 2024

Abstract Heavy metals are naturally occurring components of the Earth’s crust and persistent environmental pollutants. Human exposure to heavy occurs via various pathways, including inhalation air/dust particles, ingesting contaminated water or soil, through food chain. Their bioaccumulation may lead diverse toxic effects affecting different body tissues organ systems. The toxicity depends on properties given metal, dose, route, duration (acute chronic), extent bioaccumulation. detrimental impacts human health largely linked their capacity interfere with antioxidant defense mechanisms, primarily interaction intracellular glutathione (GSH) sulfhydryl groups (R-SH) enzymes such as superoxide dismutase (SOD), catalase, peroxidase (GPx), reductase (GR), other enzyme Although arsenic (As) is believed bind directly critical thiols, alternative hydrogen peroxide production processes have also been postulated. known signaling pathways affect a variety cellular processes, cell growth, proliferation, survival, metabolism, apoptosis. For example, cadmium can BLC-2 family proteins involved in mitochondrial death overexpression antiapoptotic Bcl-2 suppression proapoptotic (BAX, BAK) thus increasing resistance cells undergo malignant transformation. Nuclear factor erythroid 2-related 2 (Nrf2) an important regulator enzymes, level oxidative stress, oxidants has shown act double-edged sword response arsenic-induced stress. Another mechanism significant threats metal (e.g., Pb) involves substitution essential calcium (Ca), copper (Cu), iron (Fe)) structurally similar (Cd) (Pb)) metal-binding sites proteins. Displaced redox (copper, iron, manganese) from natural catalyze decomposition Fenton reaction generate damaging ROS hydroxyl radicals, causing damage lipids, proteins, DNA. Conversely, some metals, cadmium, suppress synthesis nitric oxide radical (NO · ), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced stress be indirectly responsible for depletion due its (O ·− resulting formation potent biological oxidant, peroxynitrite (ONOO − ). This review comprehensively discusses mechanisms effects. Aluminum (Al), (Cd), (As), mercury (Hg), (Pb), chromium (Cr) roles development gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer’s Parkinson’s diseases), cardiovascular, cancer (e.g. renal, lung, skin, stomach) diseases discussed. A short account devoted detoxification chelation use ethylenediaminetetraacetic acid ( EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic (DMSA), 2,3-dimercapto-1-propane sulfonic (DMPS), penicillamine chelators.

Язык: Английский

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Senolytic treatment for low back pain

Science Advances, Год журнала: 2025, Номер 11(11)

Опубликована: Март 14, 2025

Senescent cells (SnCs) accumulate because of aging and external cellular stress throughout the body. They adopt a senescence-associated secretory phenotype (SASP) release inflammatory degenerative factors that actively contribute to age-related diseases, such as low back pain (LBP). The senolytics, o -vanillin RG-7112, remove SnCs in human intervertebral discs (IVDs) reduce SASP release, but it is unknown whether they can treat LBP. sparc −/− mice, with LBP, were treated orally RG-7112 single or combination treatments. Treatment reduced LBP factor removed from IVD spinal cord. also lowered degeneration scores IVDs, improved vertebral bone quality, expression markers Together, our data suggest potential disease-modifying drugs for other painful disorders linked cell senescence.

Язык: Английский

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Exercise and exerkines: Mechanisms and roles in anti-aging and disease prevention

Experimental Gerontology, Год журнала: 2025, Номер 200, С. 112685 - 112685

Опубликована: Янв. 16, 2025

Язык: Английский

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Exploring the potential anti-senescence effects of soybean-derived peptide Soymetide in mice hippocampal neurons via the Wnt/β-catenin pathway

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 25, 2025

Soybean-based foods enhance cognitive functions by influencing hippocampal mechanisms. These salutary effects have so far been attributed to isoflavones present in soybeans. Considering cellular senescence contributes decline and that no specific soy-derived peptides are known for their potential mitigate senescence, we examined the efficacy of a thirteen amino acid peptide, Soymetide, on doxorubicin-induced mice model. Soymetide pretreatment lowered markers p53, p21 p16, pro-inflammatory cytokines, Senescence β-Galactosidase staining while enhancing mature neuronal marker NeuN hippocampus. This anti-senescent effect was comparable with well-known senolytic combination (dasatinib quercetin). Research indicates Wnt signaling influences our findings here demonstrate doxorubicin decreased Wnt3a, p-LRP6, Frizzled, Dishevelled, Axin1, β-catenin levels increased GSK-3β, mitigated these effects. Additionally, upon inhibition Wnt/β-catenin pathway, Soymetide's ability reduce restore expression reduced. We validated anti-senescence impact neurons co-immunostaining indicators alongside assessed it primary neurons. Further examining survival revealed blocked loss Nissl-stained surviving learning-memory performances, measured Y-Maze Passive Avoidance tests, which inhibitors could counteract. In conclusion, study identifies novel Wnt/β-catenin-linked mechanism demonstrates effectiveness reversing this process. Hence, suggests therapeutic application addressing associated aging.

Язык: Английский

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Analysis of cellular senescence-related genes in calcified aortic valve disease and the potential therapeutic role of β-Carotene

PLoS ONE, Год журнала: 2025, Номер 20(3), С. e0318574 - e0318574

Опубликована: Март 10, 2025

Objective Calcific aortic valve disease (CAVD) is a progressive, age-related degenerative characterized by the accumulation of calcium deposits in valve. We aim to screen key genes associated with cellular senescence (CS) CAVD. Methods The GSE12644 and GSE51472 datasets from GEO database was utilized this study, differentially expressed (DEGs) were identified using “ limma ” R package. CS-related DEGs (CS-DEGs) determined through CellAge database. Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analyses performed on CS-DEGs. A protein–protein interaction (PPI) network constructed STRING cytoHubba plug-in Cytoscape used identify hub genes. noncoding-RNA-mRNA regulatory established. DSigDB drugs potentially be useful for treating Results total 16 CS-DEGs identified. These primarily collagen metabolic process, catabolic process external side plasma membrane. 10 as regulators CAVD: LPAR1, PTPN6, CD28, ID1, MEIS2, FGFR3, KDR, MMP7, AR, HIF1A. Noncoding RNA-mRNA indicated that may regulated noncoding RNAs. β-Carotene, naturally occurring carotenoid antioxidant properties, potential therapeutic agents interacting MMP9, CTSB. Conclusion This study provides insights into pathways related CAVD (MMP9, CTSB) highlights role β-Carotene treatment

Язык: Английский

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The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(2), С. 386 - 386

Опубликована: Янв. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Язык: Английский

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Neuroinflammaging and the Immune Landscape: The Role of Autophagy and Senescence in Aging Brain

Biogerontology, Год журнала: 2025, Номер 26(2)

Опубликована: Фев. 5, 2025

Abstract Neuroinflammation is closely linked to aging, which damages the structure and function of brain. It caused by intricate interactions immune cells in aged brain, such as dysregulated glial dysfunctional astrocytes. Aging-associated chronic low inflammation, referred neuroinflammaging, shows an upregulated proinflammatory response. Autophagy senescence play crucial roles moderators aging neuroinflammatory responses. The neuroimmune system, dystrophic cells, release factors alter blood-brain barrier, causing a landscape. Chronic inflammation combined with deteriorating neurons exacerbate neurological disorders decline cognitive function. This review highlights neuroinflammaging mechanism associated interplay central nervous system cellular senescence, autophagy regulation brain's under conditions. Moreover, microglia peripheral process brain have also been discussed. Determining treatment targets comprehending mechanisms that influence necessary decrease neuroinflammation.

Язык: Английский

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Cellular Senescence in Health, Disease, and Lens Aging

Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 244 - 244

Опубликована: Фев. 12, 2025

Background: Cellular senescence is a state of irreversible cell cycle arrest that serves as critical regulator tissue homeostasis, aging, and disease. While transient contributes to development, wound healing, tumor suppression, chronic drives inflammation, dysfunction, age-related pathologies, including cataracts. Lens epithelial cells (LECs), essential for maintaining lens transparency, are particularly vulnerable oxidative stress-induced senescence, which accelerates aging cataract formation. This review examines the dual role in LEC function its implications cataractogenesis, alongside emerging senotherapeutic interventions. Methods: synthesizes findings on molecular mechanisms focusing stress, mitochondrial senescence-associated secretory phenotype (SASP). It explores evidence linking formation, highlighting key studies stress responses, DNA damage, antioxidant defense. Recent advances senotherapeutics, senolytics senomorphics, analyzed their potential mitigate delay progression. Conclusions: driven by impaired redox homeostasis. These factors activate path-ways, p53/p21 p16/Rb, resulting SASP-mediated inflammation. The accumulation senescent LECs reduces regenerative capacity, disrupts cataractogenesis. Emerging such dasatinib, quercetin, metformin, show promise reducing burden modulating SASP preserve transparency.

Язык: Английский

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The Advancements of Marine Natural Products in the Treatment of Alzheimer’s Disease: A Study Based on Cell and Animal Experiments

Marine Drugs, Год журнала: 2025, Номер 23(3), С. 91 - 91

Опубликована: Фев. 20, 2025

As life expectancy rises and the aging population grows, Alzheimer’s disease (AD) has become a significant global health concern. AD is complex neurodegenerative disorder with an unclear etiology. Current hypotheses primarily focus on β-amyloid (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation as key pathological processes. Given limited efficacy of existing therapeutic strategies, there urgent need to explore novel treatment options. Marine natural products have garnered attention due their unique chemical structures diverse bioactivities, demonstrating potential for multi-target interventions in AD. This review systematically summarizes roles marine-derived compounds, including polysaccharides, carotenoids, polyphenols, modulating Aβ mitigating pathology, regulating gut–brain axis dysfunction. Furthermore, challenges current research are discussed, emphasis improving blood–brain barrier permeability optimizing drug delivery systems facilitate clinical translation.

Язык: Английский

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Impact of Disease-Modifying Antirheumatic Drugs on Cognitive Function in Older Adults with Rheumatoid Arthritis

Drugs & Aging, Год журнала: 2025, Номер unknown

Опубликована: Март 15, 2025

Cognitive impairment poses significant challenges for aging populations. Systemic inflammation, a hallmark of rheumatoid arthritis (RA), has been implicated in neurodegeneration through mechanisms including blood–brain barrier disruption, microglial activation, and cytokine-mediated neuronal damage. This review examines the potential impact disease-modifying antirheumatic drugs (DMARDs) on cognitive function RA, focusing inflammatory pathways linking systemic inflammation to neuroinflammation decline. DMARDs, categorized into conventional synthetic (csDMARDs), biologic (bDMARDs), targeted (tsDMARDs) classes, modulate immune responses distinct mechanisms. Evidence suggests that particularly bDMARDs targeting proinflammatory cytokines such as TNF-α IL-6, may mitigate neuroinflammatory processes preserve function. However, csDMARDs methotrexate is complex, with conflicting reports regarding its role vascular dementia. Emerging therapies Janus kinase inhibitors (JAK-i) offer promise modulating central though clinical evidence remains limited. While some studies highlight protective effects DMARDs against dementia, findings are inconsistent, hindered by heterogeneity study design, patient demographics, assessment methods. underscores need personalized treatment strategies, integrating RA management health considerations. Future research should prioritize robust, prospective long-term follow-up, incorporating neuroimaging biomarker analysis elucidate underpinning DMARD-associated outcomes. A better understanding involved could lead improved therapeutic approaches, enhancing quality life patients potentially benefiting broader strategies preventing or treating

Язык: Английский

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