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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Natural dietary ROS scavenger-based nanomaterials for ROS-related chronic disease prevention and treatment

Chemical Engineering Journal, Год журнала: 2024, Номер 490, С. 151756 - 151756

Опубликована: Апрель 30, 2024

Язык: Английский

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Targeting natural antioxidant polyphenols to protect neuroinflammation and neurodegenerative diseases: a comprehensive review

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Янв. 24, 2025

Polyphenols, naturally occurring phytonutrients found in plant-based foods, have attracted significant attention for their potential therapeutic effects neurological diseases and neuroinflammation. These compounds possess diverse neuroprotective capabilities, including antioxidant, anti-inflammatory, anti-amyloid properties, which contribute to mitigating the progression of neurodegenerative conditions such as Alzheimer's Disease (AD), Parkinson's (PD), Dementia, Multiple Sclerosis (MS), Stroke, Huntington's (HD). Polyphenols been extensively studied ability regulate inflammatory responses by modulating activity pro-inflammatory genes influencing signal transduction pathways, thereby reducing neuroinflammation neuronal death. Additionally, polyphenols shown promise various cellular signaling pathways associated with viability, synaptic plasticity, cognitive function. Epidemiological clinical studies highlight polyphenol-rich diets decrease risk alleviate symptoms disorders Furthermore, demonstrated through regulation key Akt, Nrf2, STAT, MAPK, play critical roles neuroprotection body's immune response. This review emphasizes growing body evidence supporting combating neurodegeneration neuroinflammation, well enhancing brain health. Despite substantial promising hypotheses, further research investigations are necessary fully understand role establish them advanced targets age-related neuroinflammatory conditions.

Язык: Английский

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Curcumin nanoparticles alleviate brain mitochondrial dysfunction and cellular senescence in γ-irradiated rats

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 31, 2025

Despite the diverse applications of γ radiation in radiotherapy, industrial processes, and sterilization, it causes hazardous effects on living organisms, such as cellular senescence, persistent cell cycle arrest, mitochondrial dysfunction. This study evaluated efficacy curcumin nanoparticles (CNPs) mitigating dysfunction senescence induced by rat brain tissues. Four groups male Wistar albino rats (n = 8 per group) were included: (Gr1) control group; (Gr2) CNPs group (healthy receiving oral administration at a dose 10 mg/kg/day, three times week for eight weeks); (Gr3) irradiated (rats exposed to single Gy head irradiation); (Gr4) + (irradiated treated with CNPs). The data obtained demonstrated that weeks attenuated oxidative stress γ-irradiated lowering brain's lipid peroxidation level [malondialdehyde (MDA)] enhancing antioxidant markers [superoxide dismutase (SOD), reduced glutathione (GSH), total capacity (TAC)] (P < 0.05). In addition, significantly increased function improving complex I, II, ATP production levels compared group. rats, also showed anti-neuroinflammatory reducing interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-ĸB) Moreover, administered β-galactosidase activity expression p53, p21, p16 genes 0.05) while concurrently inducing significant increase AMPK mRNA conclusion, ameliorated neurotoxicity hold promise novel agent delay via their combined antioxidant, anti-inflammatory, mitochondrial-enhancing properties.

Язык: Английский

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Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment

Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102480 - 102480

Опубликована: Сен. 3, 2024

Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen nitrogen species (ROS RNS). The associated progressive accumulation molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger indirect antioxidant, is synthesized matrix neurons. Melatonin reduces ETC elevates ATP production; it also detoxifies ROS/RNS via SIRT3/FOXO pathway upregulates activities superoxide dismutase 2 glutathione peroxidase. influences glucose processing by In neurogenerative diseases, often adopt Warburg-type metabolism which excludes pyruvate mitochondria causing reduced acetyl coenzyme A production. Acetyl supports citric acid cycle OXPHOS. Additionally, required co-substrate for arylalkylamine-N-acetyl transferase, rate limits melatonin synthesis; therefore, production diminished cells that experience making more vulnerable stress. Moreover, endogenously produced diminishes during aging, further increasing components. More normal preserved aging with supplementation.

Язык: Английский

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Neurodegenerative diseases and catechins: (−)-epigallocatechin-3-gallate is a modulator of chronic neuroinflammation and oxidative stress

Frontiers in Nutrition, Год журнала: 2024, Номер 11

Опубликована: Авг. 1, 2024

Catechins, a class of phytochemicals found in various fruits and tea leaves, have garnered attention for their diverse health-promoting properties, including potential combating neurodegenerative diseases. Among these catechins, (-)-epigallocatechin-3-gallate (EGCG), the most abundant polyphenol green tea, has emerged as promising therapeutic agent due to its potent antioxidant anti-inflammatory effects. Chronic neuroinflammation oxidative stress are key pathological mechanisms diseases such Alzheimer's disease (AD) Parkinson's (PD). EGCG neuroprotective efficacy scavenging free radicals, reducing attenuating neuroinflammatory processes. This review discusses molecular EGCG's anti-oxidative chronic neuroinflammation, emphasizing effects on autoimmune responses, neuroimmune system interactions, focusing related AD PD. By elucidating action impact processes, this underscores intervention AD, PD, possibly other Overall, emerges natural compound stress, offering novel avenues strategies treatment disorders.

Язык: Английский

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Exosome-equipped TNF antisense oligodeoxynucleotide or 2-deoxy-D-glucose ameliorated nonalcoholic steatohepatitis by modulating superoxide dismutase 1 in mice

Redox Biology, Год журнала: 2025, Номер 80, С. 103488 - 103488

Опубликована: Янв. 5, 2025

Inflammatory mediators tumor necrosis factor (TNF) and interleukin 1 beta (IL1β), primarily derived from hepatic macrophages in the liver, play a crucial role progression of nonalcoholic steatohepatitis (NASH). Meanwhile, intravenously injected exosomes are mainly distributed liver predominantly taken up by macrophage. Herein, we aimed to evaluate feasibility targeted inhibition TNF IL1β expression via as potential therapeutic strategy for NASH. In this study, demonstrated that antisense oligodeoxynucleotide targeting (ASO-TNF) or 2-deoxy-d-glucose (2DG) effectively suppressed and/or macrophages. Exosomes loaded with ASO-TNF 2DG were able suppress vitro vivo. Furthermore, infusion Exo/ASO-TNF Exo/2DG significantly attenuated experimental choline deficient amino acid-defined (CDAA) methionine (MCD) diet-fed mice. RNA-seq results showed treatment inhibited pro-inflammatory signaling pathways. Mechanistically, observed administration could attenuate NASH up-regulating superoxide dismutase (Sod1). Combined, our findings alleviated murine models. Thus, anti-inflammatory agents holds promise treatment.

Язык: Английский

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Toxicology of aspartame to largemouth bass (Micropterus salmoides) on the basis of antioxidant capacity, liver histology and the interstinal microbiota

Animal Feed Science and Technology, Год журнала: 2025, Номер unknown, С. 116225 - 116225

Опубликована: Янв. 1, 2025

Язык: Английский

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From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease

Annals of Hepatology, Год журнала: 2025, Номер unknown, С. 101777 - 101777

Опубликована: Янв. 1, 2025

Non-alcoholic fatty liver disease (NAFLD), now recognized as metabolic dysfunction-associated steatotic (MASLD), represents a significant and escalating global health challenge. Its prevalence is intricately linked to obesity, insulin resistance, other components of the syndrome. As our comprehension MASLD deepens, it has become evident that this condition extends beyond liver, embodying complex, multi-systemic with hepatic manifestations mirror broader landscape. This comprehensive review delves into critical interplay between gut-liver axis oxidative stress, elucidating their pivotal roles in etiology progression MASLD. Our analysis reveals several key findings: (1) Bile acid dysregulation can trigger stress through enhanced ROS production hepatocytes Kupffer cells, leading mitochondrial dysfunction lipid peroxidation; (2) Gut microbiota dysbiosis disrupts intestinal barrier function, allowing increased translocation endotoxins like LPS, which activate inflammatory pathways TLR4 signaling promote via NADPH oxidase activation; (3) The redox-sensitive transcription factors NF-κB Nrf2 serve crucial mediators axis, regulating responses orchestrating antioxidant defenses; (4) Oxidative stress-induced damage function creates destructive feedback loop, further exacerbating inflammation progression. These findings highlight complex interrelationship pathogenesis, suggesting potential therapeutic targets for management.

Язык: Английский

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Exploring Strategies to Prevent and Treat Ovarian Cancer in Terms of Oxidative Stress and Antioxidants

Antioxidants, Год журнала: 2025, Номер 14(1), С. 114 - 114

Опубликована: Янв. 20, 2025

Oxidative stress is a state of imbalance between the production reactive oxygen species (ROS) and nitrogen (RNS) antioxidant defence system in body. may be associated with variety diseases, such as ovarian cancer, diabetes mellitus, neurodegeneration. The generation oxidative one common refractory malignancies among gynaecological tumours, several factors. On hand, increased metabolism cancer cells can lead to ROS, on other impaired not able effectively scavenge excessive ROS. In addition, chemotherapy radiotherapy elevate cells. cause damage, promote development even result drug resistance. Therefore, studying important for prevention treatment cancer. Antioxidants, markers stress, might serve strategies preventing treating this review, we will discuss complex relationship well role therapeutic potential antioxidants thus guiding future research clinical interventions.

Язык: Английский

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