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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Beyond the Hayflick limit: How microbes influence cellular aging

Ageing Research Reviews, Год журнала: 2025, Номер 104, С. 102657 - 102657

Опубликована: Янв. 7, 2025

Язык: Английский

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Hypoxia-inducible factor and cellular senescence in pulmonary aging and disease

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

Опубликована: Фев. 26, 2025

Abstract Cellular senescence and hypoxia-inducible factor (HIF) signaling are crucial in pulmonary aging age-related lung diseases such as chronic obstructive disease idiopathic fibrosis cancer. HIF plays a pivotal role cellular adaptation to hypoxia, regulating processes like angiogenesis, metabolism, inflammation. Meanwhile, leads irreversible cell cycle arrest, triggering the senescence-associated secretory phenotype which contributes inflammation, tissue remodeling, fibrosis. Dysregulation of these pathways accelerates progression by promoting oxidative stress, mitochondrial dysfunction, epigenetic alterations. Recent studies indicate that interact at multiple levels, where can both induce suppress senescence, depending on conditions. While transient activation supports repair stress resistance, dysregulation exacerbates pathologies. Furthermore, emerging evidence suggests targeting could offer new therapeutic strategies mitigate diseases. This review explores intricate crosstalk between mechanisms, shedding light how their interplay influences progression. Additionally, we discuss potential interventions, including senolytic therapies modulators, enhance health longevity.

Язык: Английский

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Neuronal cell cycle reentry events in the aging brain are more prevalent in neurodegeneration and lead to cellular senescence

PLoS Biology, Год журнала: 2024, Номер 22(4), С. e3002559 - e3002559

Опубликована: Апрель 23, 2024

Increasing evidence indicates that terminally differentiated neurons in the brain may recommit to a cell cycle-like process during neuronal aging and under disease conditions. Because of rare existence random localization these cells brain, their molecular profiles disease-specific heterogeneities remain unclear. Through bioinformatics approach allows integrated analyses multiple single-nucleus transcriptome datasets from human samples, populations were identified selected for further characterization. Our indicated cycle-related events occur predominantly excitatory cellular senescence is likely immediate terminal fate. Quantitatively, number cycle re-engaging senescent decreased normal process, but context late-onset Alzheimer's (AD), accumulate instead. Transcriptomic profiling suggested differences tied early stage revealing presented more proinflammatory, metabolically deregulated, pathology-associated signatures disease-affected brains. Similarly, general features also observed subpopulation dopaminergic Parkinson's (PD)-Lewy body dementia (LBD) model. An extended analysis conducted mouse model validated ability this determine robust relationship between processes cross-species setting.

Язык: Английский

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PM2.5 Induces Cardiomyoblast Senescence via AhR-Mediated Oxidative Stress

Antioxidants, Год журнала: 2024, Номер 13(7), С. 786 - 786

Опубликована: Июнь 28, 2024

Previous research has established a correlation between PM2.5 exposure and aging-related cardiovascular diseases, primarily in blood vessels. However, the impact of on cardiomyocyte aging remains unclear. In this study, we observed that extractable organic matter (EOM) from led to cellular senescence H9c2 cardiomyoblast cells, as characterized by an increase percentage β-galactosidase-positive elevated expression levels p16 p21, enhanced H3K9me3 foci. EOM also induced cell cycle arrest at G1/S stage, accompanied downregulation CDK4 Cyclin D1. Furthermore, significant elevation intracellular reactive oxygen species (ROS), mitochondrial ROS, DNA damage. Supplementation with antioxidant NAC effectively attenuated EOM-induced cardiac senescence. Our findings revealed activated aryl hydrocarbon receptor (AhR) signaling pathway, evidenced AhR translocation nucleus upregulation Cyp1a1 Cyp1b1. Importantly, antagonist CH223191 mitigated oxidative stress conclusion, our results indicate PM2.5-induced activation leads stress, damage, arrest, leading Targeting AhR/ROS axis might be promising therapeutic strategy for combating aging.

Язык: Английский

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LILRB2 inhibition enhances radiation sensitivity in non-small cell lung cancer by attenuating radiation-induced senescence

Cancer Letters, Год журнала: 2024, Номер 593, С. 216930 - 216930

Опубликована: Май 3, 2024

Radiotherapy (RT) in non-small cell lung cancer (NSCLC) triggers cellular senescence, complicating tumor microenvironments and affecting treatment outcomes. This study examines the role of lymphocyte immunoglobulin-like receptor B2 (LILRB2) modulating RT-induced senescence radiosensitivity NSCLC. Through methodologies including irradiation, lentivirus transfection, various molecular assays, we assessed LILRB2's expression its impact on levels behaviors. Our findings reveal that RT upregulates LILRB2, facilitating a senescence-associated secretory phenotype (SASP), which turn enhances proliferation resistance to radiation. Importantly, LILRB2 silencing attenuates these effects by inhibiting JAK2/STAT3 pathway, significantly increasing NSCLC models. Clinical data correlate high with reduced response poorer prognosis, suggesting pivotal potential as therapeutic target improve radiosensitivity.

Язык: Английский

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Cellular senescence: from homeostasis to pathological implications and therapeutic strategies

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 3, 2025

Cellular aging is a multifactorial and intricately regulated physiological process with profound implications. The interaction between cellular senescence cancer complex multifaceted, can both promote inhibit tumor progression through various mechanisms. M6A methylation modification regulates the of cells tissues by modulating senescence-related genes. In this review, we comprehensively discuss characteristics senescence, signaling pathways regulating biomarkers mechanisms anti-senescence drugs. Notably, review also delves into interactions cancer, emphasizing dual role senescent microenvironment in initiation, progression, treatment. Finally, thoroughly explore function mechanism m6A revealing its critical gene expression maintaining homeostasis. conclusion, provides comprehensive perspective on molecular biological significance offers new insights for development strategies.

Язык: Английский

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The Role of Hypoxia in Longevity

Aging and Disease, Год журнала: 2025, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2025

Aging is marked by a progressive decrease in physiological function and reserve capacity, which results increased susceptibility to diseases. Understanding the mechanisms of driving aging crucial for extending health span promoting human longevity. Hypoxia, reduced oxygen availability, has emerged as promising area study within research. This review explores recent findings on potential restriction promote healthy extend lifespan. While role hypoxia-inducible factor 1 (HIF-1) cellular responses hypoxia well-established, its impact lifespan remains complex context-dependent. Investigations invertebrate models suggest HIF-1 longevity, while evidence mammalian limited. Hypoxia extends independent dietary (DR), known intervention underlying However, both DR converge common downstream effectors, such forkhead box O (FOXO) flavin-containing monooxygenase (FMOs) modulate Further work required elucidate molecular hypoxia-induced longevity optimize clinical applications. crosstalk between other longevity-associated pathways developing interventions enhance healthspan. Future studies may uncover novel therapeutic strategies populations.

Язык: Английский

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Effects of PARP1 inhibitor PJ-34 on TGFα, IL-6, and IL-1β levels in diabetic nephropathy

The Journal of Immunology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Abstract Diabetic nephropathy is a severe chronic complication characterized by cytotoxicity, inflammation, and fibrosis, ultimately leading to renal failure. This study systematically investigated the effects of PARP1 inhibitor PJ-34 on high glucose–induced fibrosis in HK-2 cells, as well its improvement neuropathic pain response transforming growth factor β (TGFβ) expression type 1 diabetes mellitus diabetic mouse model. Through cellular animal experiments, we observed that significantly enhanced proliferative capacity cells damaged glucose, reduced apoptosis, decreased release proinflammatory factors TGFα, interleukin-6, interleukin-1β. In model, administration substantially improved parameters pain, alleviated tissue damage, indicators functional impairment–inhibited key protein epithelial-mesenchymal transition process, acting through regulation TGFβ/Smads signaling pathway. elucidated mechanism action potential therapeutic agent for nephropathy, offering novel strategy treatment.

Язык: Английский

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ИНФЛАМЕЙДЖИНГ: РОЛЬ СЕНЕСЦЕНТНЫХ КЛЕТОК В ПАТОГЕНЕЗЕ ОСТЕОАРТРИТА

Успехи геронтологии, Год журнала: 2025, Номер 37(6), С. 777 - 786

Опубликована: Фев. 20, 2025

Язык: Русский

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