Biometals最新文献

{"title":"Zinc-regulated growth, chlorophyll, and antioxidant activity drive biofortification in rice varieties","authors":"Hafiza Ammara,&nbsp;Asma Zulfiqar,&nbsp;Ammara Saleem,&nbsp;Rehana Sardar,&nbsp;Usman Zulfiqar,&nbsp;Muhammad Aown Sammar Raza,&nbsp;Muhammad Faisal Maqsood,&nbsp;Hossam S. El-Beltagi,&nbsp;Mashael Daghash Alqahtani","doi":"10.1007/s10534-025-00768-5","DOIUrl":"10.1007/s10534-025-00768-5","url":null,"abstract":"<div><p>Zinc (Zn) is an essential micronutrient that plays a crucial role in numerous physiological and biochemical processes in plants, including enzyme activation, protein synthesis, chlorophyll formation, carbohydrate metabolism, and auxin regulation. Zinc biofortification cahas emerged as an effective strategy to alleviate Zn deficiency by enhancing antioxidant production, improving crop productivity and increasing Zn bioaccumulation in edible tissues. This study evaluated the effects of different concentrations of ZnSO₄ (100, 200, 300, 400, and 500 mM) on growth and performance and osmolyte production (protein and soluble sugars) in two rice (<i>Oryza sativa</i>) varieties. The results showed that Zn concentrations up to 400 mM significantly improved biochemical parameters—protein concentration (by 17.961%), soluble sugar levels (by 13%), and chlorophyll activity (by 45%)—as well as physiological attributes such as plant height (by 9.64%), leaf length (by 163.29%), and leaf width (by 114.759%). Additionally, moderate Zn application reduced H₂O₂ accumulation in rice and enhanced the activity of antioxidant enzymes including catalase (CAT, 30.02%), malondialdehyde (MDA, 34%), and ascorbate peroxidase (APX, 40.958%). However, higher Zn concentrations exerted toxic effects, resulting in reduced growth and biochemical performance. Overall, the findings demonstrate that optimal ZnSO₄ application can increase Zn content by 5–18% and enhance the nutritional and physiological quality of rice cultivated under Zn-deficient conditions. Moderate Zn application improves growth, antioxidant activity, and nutritional quality in rice, whereas excessive Zn concentrations exert toxic effects. These findings support Zn biofortification as a sustainable strategy to enhance crop productivity and nutritional value under Zn-deficient conditions.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"375 - 388"},"PeriodicalIF":3.6,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The different affinity of the two metal-binding sites of human ferroportin drives outward directionality of transport","authors":"Matteo Amadei,&nbsp;Alfredo De Lauro,&nbsp;Fabio Polticelli,&nbsp;Giovanni Musci,&nbsp;Maria Carmela Bonaccorsi di Patti","doi":"10.1007/s10534-025-00763-w","DOIUrl":"10.1007/s10534-025-00763-w","url":null,"abstract":"","PeriodicalId":491,"journal":{"name":"Biometals","volume":"38 6","pages":"2075 - 2076"},"PeriodicalIF":3.6,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10534-025-00763-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rice bran extract ameliorates metal mixture induced cerebral cortex dysfunction: implicating the Nrf-2/HMOX-1/BDNF signalling pathway","authors":"Baridoo Donatus Dooka,&nbsp;Chinna N. Orish,&nbsp;Anthonet N. Ezejiofor,&nbsp;Theresa Umeji,&nbsp;Kpobari W. Nkpaa,&nbsp;Ifeoma Okereke,&nbsp;Ana Cirovic,&nbsp;Aleksandar Cirovic,&nbsp;Orish E. Orisakwe","doi":"10.1007/s10534-025-00765-8","DOIUrl":"10.1007/s10534-025-00765-8","url":null,"abstract":"<div><p>Exposure to heavy metal mixtures (MM) pose significant public health concern due to their adverse health risks. Rice bran extract (RBE) elicits antioxidants, anti-inflammatory and antiapoptotic properties. This study has evaluated the neuroprotective properties of RBE on MM induced cerebral dysfunction and its underlying cellular mechanisms. Thirty-five rats were exposed to MM alone at Pb 20 mg/kg, Al 35 mg/kg, and Mn 0.564 mg/kg body weight or co-exposed with RBE at 125, 250 and 500 mg/kg body weight, 125 RBE mg/kg b.wt only, and 500 RBE mg/kg b.wt only 5 days a week for 13 weeks (90 days). Thereafter, antioxidants, lipid peroxidation, inflammation (cyclooxygenase-2) and protein levels of occludin, amyloid precursor proteins (Aβ40 and Aβ42), apoptotic marker (caspase-3), HMOX-1, BDNF and transcription factor Nrf-2 in the cerebral cortex were investigated. Our results showed that RBE co-administration with MM reversed MM induced diminution of antioxidants and decreased lipid peroxidation, cyclooxygenase-3, caspase-3. Furthermore, our results shows that MM alone significantly increased bioaccumulation of Pb, Al, Mn in the cerebral cortex, increased levels of Aβ40, Aβ42 and Nrf-2 as well as significantly decreased BDNF, occlude in and HMOX-1 in comparison to the control. All these were reversed by RBE. Taken together, RBE abated MM-induced oxidative stress, neuronal inflammation and cerebral apoptosis via regulation of amyloid precursor proteins, BDNF, HMOX-1 via Nrf-2 dependent pathways to reversed MM induced cerebral toxicity.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"323 - 336"},"PeriodicalIF":3.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Ag and Cu additions on antibacterial performance of Fe-based amorphous alloys","authors":"Sha Yang,&nbsp;Jipeng Pan,&nbsp;Hong Zhang,&nbsp;Haibo Ling","doi":"10.1007/s10534-025-00759-6","DOIUrl":"10.1007/s10534-025-00759-6","url":null,"abstract":"<div><p>Fe-based amorphous alloys exhibit good mechanical properties, corrosion resistance, and biocompatibility, making them promising biomedical materials. However, their antibacterial performance requires improvement. This study investigates the effect of adding Ag and Cu to Fe-based amorphous alloys to enhance antibacterial properties. Three alloy samples, Fe₈₅Si₂B₉P₃C₁, Fe₈₄Si₂B₉P₃C₁Ag₁, and Fe₈₄Si₂B₉P₃C₁Cu₁, were prepared using single-roll ribbon spinning technology. The biocompatibility and antibacterial properties of these samples were compared with commercial 316L stainless steel (SS). Potentiodynamic polarization tests in Hank’s solution (pH = 7.4) and artificial saliva (pH = 6.3) revealed that adding Cu slightly reduced corrosion resistance, while Ag significantly improved it. The corrosion resistance of the amorphous alloys was better than 316L SS. Ion release tests showed that Ag and Cu alloys released Ag and Cu ions, respectively, in addition to Fe ions, with Ag showing the highest concentration. Antibacterial tests indicated that adding Ag or Cu, especially Ag, significantly improved antibacterial performance, achieving a 99.83% inhibition rate.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"259 - 267"},"PeriodicalIF":3.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic resistance dissemination in soil ecosystems: deep understanding for effective management and global health protection","authors":"Lu Li,&nbsp;Juexi Li,&nbsp;Saeed ur Rahman,&nbsp;Asad Rehman,&nbsp;Muhammad Khalid","doi":"10.1007/s10534-025-00753-y","DOIUrl":"10.1007/s10534-025-00753-y","url":null,"abstract":"<div><p>Antibiotic resistance poses a significant threat to global health, extending beyond clinical settings into environmental reservoirs such as soil, where resistant bacteria persist and evolve. Current efforts focus on understanding the origins and implications of antibiotic resistance in soil ecosystems. It defines antibiotic resistance within an environmental context and highlights soil as a critical reservoir for antibiotic-resistant genes (ARGs). Key sources of antibiotics in soil are identified, including agricultural practices, medical waste, and municipal and industrial effluents. The classification and mechanisms of ARGs are outlined, along with their transmission pathways, particularly within soil biofilms, which play a crucial role in gene transfer and microbial protection. The interplay between soil microbial communities and antibiotic resistance is discussed, emphasizing its potential risks to human health, including infectious diseases and food safety concerns. Strategies for mitigating antibiotic resistance in soil are presented, focusing on optimizing antibiotic usage, developing alternatives, and enhancing degradation mechanisms. This review underscores the need for interdisciplinary research to deepen understanding of soil microbial diversity and its connection to antibiotic resistance, emphasizing integrated efforts to safeguard soil and human health.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"59 - 83"},"PeriodicalIF":3.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological effects of p-PYA ligands on certain trace elements of group-12 towards DNA binding and cytotoxicity potency","authors":"Sara Masood,&nbsp;Bushra Nawaz,&nbsp;Kashif Javed,&nbsp;Zahid Rashid,&nbsp;Sajjad Hussain Sumrra,&nbsp;Gul-e-Saba Chaudhry,&nbsp;M. Naveed Zafar","doi":"10.1007/s10534-025-00764-9","DOIUrl":"10.1007/s10534-025-00764-9","url":null,"abstract":"<div><p>The substantial anticancer potential of inexpensive trace metal-based coordination compounds has been seen to convey enormous significance in the area of cancer therapy. Herein, the present work portrays the synthesis of four new Cd(II) and Zn(II) complexes of general formula, <span>([{text{M}}({text{L}}_{{text{R}}}^{{text{p}}} )left( {text{X}} right)_{2} ])</span><b>,</b> where M = Zn(II) or Cd(II) and X = I⁻ or Cl⁻, encompassing the pincer-shaped pyridylidene amide derivatives of <span>({text{L}}_{{text{Me }}}^{{text{p}}})</span> = N²,N⁶-bis(1-methylpyridin-4(1H)-ylidene)pyridine-2,6-dicarboxamide and <span>({text{L}}_{{{text{Bn}}}}^{{text{p}}})</span> = N²,N⁶-bis(1-benzylpyridin-4(1H)-ylidene)pyridine-2,6-dicarboxamide. The synthesized drug candidates were characterized through NMR (¹H and ¹³C), FT-IR spectroscopy and elemental analysis. Geometry optimization, frontier orbital analysis and electronic characteristics were investigated by DFT studies. Compounds 1–7 interacted with DNA, showing moderate binding affinity to CT DNA (K_b = 1.8 to 9.4 × 10⁴ M⁻¹) and stabilizing the duplex through mixed binding mechanisms, supported by molecular docking studies. Complexes (<b>4–7</b>) were determined to be stable during the examined time by using electronic spectroscopy and ¹HNMR analysis of their solutions. The MTT assay was used to evaluate the cytotoxicity of ligands and complexes. The Annexin V-FITC apoptosis detection and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays were used to assess early apoptosis and DNA fragmentation, respectively. By employing the Caspase-Glo™ assay to investigate pro-apoptotic caspase activation, the fundamental mechanism of DNA fragmentation was further clarified. The in vitro cytotoxicity of the compounds was evaluated against breast cancer cell lines (MCF-7, T47D) and the Vero cell line as a representative of normal cells. Complexes <b>6</b> (12.2 ± 0.3 µM) and <b>7</b> (10.0 ± 3.6 µM) exhibited remarkable anticancer activity compared to complexes <b>4</b> (40.0 ± 0.8 µM), <b>5</b> (29.0 ± 2.8 µM), and cisplatin (25.1 ± 1.1 µM) against the T47D cell line. Furthermore, complexes <b>6</b> and <b>7</b> induced DNA fragmentation through the initiation of early and late apoptosis, accompanied by the activation of apoptotic signaling cascades (caspase-3/7 and caspase-9), thereby confirming apoptosis as the underlying mechanism of cell death in the breast cancer cell line.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"297 - 322"},"PeriodicalIF":3.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gold nanoparticles incorporating rutin hydrate for targeting oxidative stress-driven neurodegeneration","authors":"Zanfré Ané Meyer,&nbsp;Sanjeev Rambharose","doi":"10.1007/s10534-025-00757-8","DOIUrl":"10.1007/s10534-025-00757-8","url":null,"abstract":"<div><p>Neurodegenerative disorders (NDs), exemplified by Alzheimer’s disease (AD), present a global health challenge driven by oxidative stress, with current therapies hampered by poor blood–brain barrier (BBB) permeability. In this study, green-synthesized rutin hydrate (RH)-capped metallic gold nanoparticles (RH-AuNPs) were developed and, for the first time, evaluated for stability, biocompatibility, and antioxidant potential in SH-SY5Y cells under oxidative stress, compared to conventional gold NPs (AuNPs) and free RH. Nanoparticles (NPs) were characterized using UV–Visible spectroscopy, dynamic light scattering for particle size and distribution and surface charge, Fourier transform infrared spectroscopy (FTIR) and scanning transmission electron microscopy (STEM). Their in chemico antioxidant potential was assessed via DPPH assay, while in vitro biocompatibility was evaluated using WST-1, and cellular antioxidant activity was determined using both plate-based DCF assay, fluorescence DCF microscopy, and MitoSOX microscopy to assess intracellular and mitochondrial ROS. The RH-AuNPs exhibited favourable physicochemical traits (λmax = 523 nm, size = 34.043 ± 0.041 nm, polydispersity index (PDI) = 0.391 ± 0.003, and zetapotential (ZP) = -30.23 ± 0.569 mV) and robust biocompatibility (&gt; 80% cell viability). Their antioxidant activity matched established antioxidants and significantly surpassed conventional AuNPs. Critically, in vitro studies demonstrated RH-AuNPs’ potent antioxidant radical scavenging, outperforming both AuNPs and the RH, thereby inferring their neuroprotective capabilities. RH-AuNPs represent a promising green-synthesized neurotherapeutic platform that combines antioxidant potency, biocompatibility, and ideal characteristics, which would enable downstream potential for effective BBB penetration and neuronal protection against oxidative stress.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"203 - 229"},"PeriodicalIF":3.6,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The protective effects of selenium against NLRP3-mediated inflammation and pyroptosis: mechanisms and the potential health benefits","authors":"Anatoly V. Skalny,&nbsp;Michael Aschner,&nbsp;Abel Santamaria,&nbsp;Svetlana I. Alekseenko,&nbsp;Rongzhu Lu,&nbsp;João B. T. Rocha,&nbsp;Alexandra V. Nekhorosheva,&nbsp;Viktor A. Gritsenko,&nbsp;Alexey A. Tinkov","doi":"10.1007/s10534-025-00754-x","DOIUrl":"10.1007/s10534-025-00754-x","url":null,"abstract":"<div><p>Selenium (Se) is an essential metalloid, possessing not only antioxidant but also anti-inflammatory effects. Recent studies have shown that the latter may be mediated by modulation of NLRP3 inflammasome activation, although the exact mechanisms have yet to be fully characterized. Therefore, the objective of this review is to discuss the molecular mechanisms by which Se modulates NLRP3 inflammasome activation and to examine the downstream effects on NLRP3-mediated inflammation and pyroptotic cell death. The selenoproteins S, O, M, W, and especially glutathione peroxidase (GPX) and thioredoxin reductase (TXNRD) are involved in regulation of the NLRP3 inflammasome machinery through modulation of redox homeostasis. In contrast, Se deficiency has been shown to aggravate NLRP3 inflammasome activation induced by lipopolysaccharide (LPS) treatment or exposure to organic pollutant bisphenol A (BPA). In addition to increased reactive oxygen species (ROS) generation, Se deficiency contributes to NLRP3-mediated inflammation and pyroptosis through modulation of non-coding RNA expression. In turn, Se supplementation mitigates NLRP3 inflammasome activation in liver, heart, kidneys, intestine, brain, and certain other tissues induced by LPS exposure, ischemia/reperfusion (I/R), and various xenobiotics including heavy metals and organic pollutants. This effect appears to be mediated by modulation of various components of Toll-like receptor (TLR)/nuclear factor κB (NF-κB)/NRLP3, nuclear factor erythroid 2-related factor 2 (Nrf2)/ROS/NLRP3, thioredoxin-interacting protein (TXNIP)/NLRP3 pathways, and several other mechanisms including modulation of gut microbiota with subsequent reduction of circulating LPS levels. Collectively, these findings demonstrate that the anti-inflammatory and cytoprotective effects of Se supplementation may be mediated by modulation of NLRP3 inflammasome activation.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"85 - 118"},"PeriodicalIF":3.6,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical responses of soil filamentous fungi to copper: changes in lipid and osmolyte composition","authors":"Elena V. Fedoseeva,&nbsp;Vera M. Tereshina,&nbsp;Olga A. Danilova,&nbsp;Elena A. Ianutsevich,&nbsp;Anna E. Ivanova,&nbsp;Vera A. Terekhova","doi":"10.1007/s10534-025-00760-z","DOIUrl":"10.1007/s10534-025-00760-z","url":null,"abstract":"<div><p>Structural and quantitative changes in lipid and osmolyte profiles can serve as markers of technogenic stress caused by heavy metal pollution. This study investigates the biochemical responses of common soil filamentous fungi (<i>Alternaria septospora</i>, <i>Cladosporium halotolerans</i>, <i>Fusarium equiseti</i>, <i>Trichoderma harzianum</i>, and <i>Clonostachys farinosa)</i> to copper (Cu) exposure, focusing on changes in lipids (membrane and storage lipids) and specific osmolytes (polyols and certain carbohydrates). Based on effective concentration values, <i>A. septospora</i> and <i>C. farinosa</i> proved to be the most Cu-resistant species. Under Cu stress, we observed an increased phosphatidylcholines/phosphatidylethanolamines (PC/PE) ratio in the melanized <i>A. septospora</i>, <i>C. halotolerans</i>, and the resistant <i>C. farinosa</i>. Conversely, Cu exposure led to an increased proportion of phosphatidic acids in <i>T. harzianum</i>. Changes in osmolyte composition included elevated mannitol levels, alongside reduced levels of low molecular weight polyols (arabitol, erythritol) and carbohydrates, primarily trehalose. The increased PC/PE ratio, elevated mannitol, and reduced low molecular weight polyols may serve as reliable indicators of Cu-induced stress. These findings underscore the pivotal role of lipid and osmolyte remodeling in fungal tolerance to copper stress and suggest their potential utility as biochemical markers for assessing environmental heavy metal contamination and guiding bioremediation strategies.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"269 - 283"},"PeriodicalIF":3.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From environmental exposure to retinal pathology: epidemiological and mechanistic insights into multi-metal driven ocular diseases","authors":"Yating Zhou,&nbsp;Chen Liu,&nbsp;Jian Yin,&nbsp;Dandan Zhao,&nbsp;Fei Xue","doi":"10.1007/s10534-025-00756-9","DOIUrl":"10.1007/s10534-025-00756-9","url":null,"abstract":"<div><p>With aging and environmental pollution, heavy metal exposure has become a growing concern for age-related eye diseases. However, the relationship between heavy metals and age-related macular degeneration (AMD), cataracts, glaucoma, and diabetic retinopathy (DR) remains unclear. This study investigates the association between urinary heavy metals and these eye diseases, focusing on the molecular mechanisms of cadmium (Cd) in driving AMD. Data from the 2005–2008 NHANES (n = 1865) were analyzed using multivariable logistic regression, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), restricted cubic spline (RCS) modeling, and sensitivity analyses. Potential molecular mechanisms of Cd in AMD were explored via intersection gene screening, protein–protein interaction network construction, and GO/KEGG enrichment analyses. In single-metal exposure models, Cd was significantly associated with AMD (OR = 1.563, 95% CI: 1.177–2.077, P = 0.00205), Co with cataract (OR = 1.386), U with glaucoma (OR = 1.300), and As with DR (OR = 1.214). In the WQS model, only AMD remained significantly associated with the overall metal mixture (OR = 1.89, 95% CI: 1.22–2.91, P = 0.0041). BKMR identified Cd as the most influential contributor to AMD (PIP = 0.523). The exposure–response curve for Cd and AMD demonstrated an upward trend, with the risk of AMD increasing as Cd exposure levels rose. Additionally, the overall metal mixture was positively associated with AMD risk. Subgroup and RCS analyses confirmed the stability of results, with no significant interaction across demographic subgroups. Sensitivity analyses further validated the findings: the highest quartile of Cd exposure was associated with increased AMD risk (OR = 2.45), and a significant dose–response trend was observed (P for trend = 0.0187). The association remained robust after excluding outliers (OR = 1.31, P = 0.0483).Mechanistically, Cd may induce retinal pigment epithelium damage via oxidative stress (SIRT1/TP53 axis), inflammation (TLR4/NF-κB pathway and pro-inflammatory cytokines), dysregulated apoptosis (BCL2/BAX imbalance), and hypoxia-induced metabolic disruption (HIF-1 signaling). Cd is an independent risk factor for AMD, likely acting through multiple toxic pathways. The effects of U, Co, and As may depend on exposure thresholds or confounders. These findings highlight the need for stricter Cd control and targeted antioxidant or anti-inflammatory strategies for age-related eye disease prevention and treatment.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"39 1","pages":"181 - 202"},"PeriodicalIF":3.6,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145327960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}