Toxicology letters最新文献

{"title":"Involvement of mitochondrial dysfunction and oxidative stress in the nephrotoxicity induced by high-fat diet in Sprague-Dawley rats","authors":"Bin Zhang,&nbsp;Jianfang Xu,&nbsp;Mengdie Wang,&nbsp;Chang Yu","doi":"10.1016/j.toxlet.2025.01.004","DOIUrl":"10.1016/j.toxlet.2025.01.004","url":null,"abstract":"<div><div>The prevalence of obesity-associated kidney injury has increased, yet the precise extent of the injury and its underlying mechanisms remain unclear. This study used a Sprague-Dawley (SD) rat model to simulate human exposure scenarios, with the objective of investigating the involvement of mitochondria in obesity-induced renal toxicity. Biochemical analysis revealed significant increases in serum creatinine, cystatin C, urinary protein, urinary microalbumin, and urinary α1-microglobulin levels in rats fed a high-fat diet, indicating a notable decline in glomerular filtration function. Histopathological examination showed mild to moderate degeneration in renal tubular epithelial cells, slight glomerular enlargement, fusion and disappearance of pedunculated cell, and decreased electron density of mitochondrial matrix and cristae, indicating the impaired filtration function of kidney. Furthermore, the study found reduced mitochondrial membrane potential and superoxide dismutase (SOD) levels, along with increased malondialdehyde (MDA) levels, signifying elevated mitochondrial oxidative stress in the kidneys of high-fat diet-fed rats. Additionally, a decrease in the number of mitochondrial uncoupling protein-2 (UCP-2) and proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)-positive cells, as well as reduced protein expression levels in the mitochondria, suggests a reduced renal mitochondrial resistance to oxidative stress. Collectively, these findings indicate that a high-fat diet triggers abnormalities in both renal filtration and structural functionality in SD rats. The observed reduction in renal mitochondrial density and the elevation in oxidative stress levels could potentially serve as underlying mechanisms.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"404 ","pages":"Pages 28-36"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of occupational aluminum exposure on blood pressure and blood glucose in workers – A longitudinal study in northern China","authors":"Lingshan Xue ,&nbsp;Shihui Guo ,&nbsp;Jiaping Huan ,&nbsp;Chenyang Li ,&nbsp;Jing Song ,&nbsp;Linping Wang ,&nbsp;Huifang Zhang ,&nbsp;Baolong Pan ,&nbsp;Qiao Niu ,&nbsp;Xiaoting Lu ,&nbsp;Jinzhu Yin","doi":"10.1016/j.toxlet.2025.01.005","DOIUrl":"10.1016/j.toxlet.2025.01.005","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Trace element and metal exposure is closely related to the occurrence of chronic diseases, particularly affecting blood pressure and blood glucose. Current studies suggest that heavy metal exposure is a risk factor for hypertension and diabetes. Aluminum can enter the human body through daily life and occupational exposure from food, environment, drugs, and other sources, affecting the cardiovascular, endocrine, and other systems. Therefore, it is significant to observe the effect of aluminum on blood pressure and blood glucose in workers with high concentration.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;In this study, electrolytic workers naturally exposed to high concentrations of aluminum were selected. The aim of the 5-year cohort study was to investigate the effects of continuous occupational aluminum exposure on blood pressure and blood glucose in workers and to assess the risk of potential cardiovascular and metabolic diseases due to heavy metal exposure.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In 2014, 183 participants from an electrolysis workshop at an aluminum plant in Shanxi were enrolled. Inductively coupled plasma mass spectrometry (ICP-MS) was performed to determine the plasma aluminum (P-Al) concentration of the workers and measured their blood pressure and glucose levels. At the 2019 follow-up, all parameters were measured again in the same workers. The relationship of the P-Al concentration with blood pressure and glucose levels was assessed using generalized linear regression, and risks of developing hypertension and hyperglycemia (diabetes or pre-diabetes) due to Al exposure were assessed using binary logistic regression. Dose-response relationships between average annual rates of change in P-Al and average annual rates of change in blood pressure and blood glucose were analyzed using RCS. The relative risk (RR) and attributable risk (AR) were also calculated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Generalized linear regression showed that the average annual rate of change in P-Al concentration was positively correlated with the annual rates of change in SBP, DBP, and blood glucose levels, with each e-fold increase in P-Al concentration increasing the annual rates of change in SBP and DBP by 3.55 % (&lt;em&gt;P&lt;/em&gt; &lt; 0.01) and 3.43 % (&lt;em&gt;P&lt;/em&gt; = 0.03), respectively. Binary logistic regression showed that as the average annual rate of change in P-Al concentration (categorical variable) increased, the risk of developing hypertension increased (P&lt;sub&gt;trend&lt;/sub&gt; &lt; 0.05). The RCS results showed that the relationship between the average annual rate of change in P-Al and the average annual rate of change in SBP was a showed a dose-response relationship (&lt;em&gt;P&lt;/em&gt; for overall association&lt;0.05). RR and AR increased with increasing P-Al concentration in both hypertensive and diabetic patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Persistent occupational aluminum exposure is associated with elevated blood ","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"404 ","pages":"Pages 47-57"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binding of ligands to the aryl hydrocarbon receptor: An overview of methods","authors":"Jiří Hrubý,&nbsp;Zdeněk Dvořák","doi":"10.1016/j.toxlet.2025.01.003","DOIUrl":"10.1016/j.toxlet.2025.01.003","url":null,"abstract":"<div><div>The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which plays numerous and pivotal roles in human physiology and pathophysiology. Therefore, pharmacotherapeutic targeting of the AhR is a highly pertinent issue. The identification of new AhR ligands and the characterization of the interactions between the AhR ligands and AhR protein requires appropriate methodology. In spite the AhR is monomeric intracellular soluble receptor, the full-length human AhR protein has not been crystallized so far, and its isolation in a form applicable in the binding assays is highly challenging. Recent advances, including crystallization of AhR fragments, recombinant protein technologies, and cryogenic electron microscopy, allowed for exploitation of diverse experimental techniques for studying interactions between ligands and the AhR. In the current paper, we review existing AhR ligand binding assays, including their description, applicability and limitations.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"404 ","pages":"Pages 37-46"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging nicotine analog 6-methyl nicotine increases reactive oxygen species in aerosols and cytotoxicity in human bronchial epithelial cells","authors":"Felix Effah ,&nbsp;Yehao Sun ,&nbsp;Alan Friedman ,&nbsp;Irfan Rahman","doi":"10.1016/j.toxlet.2025.01.007","DOIUrl":"10.1016/j.toxlet.2025.01.007","url":null,"abstract":"<div><div>Nicotine-contained e-cigarettes (E-cigs) generate reactive oxygen species (ROS), volatile organic compounds, and heavy metals. Inhalation toxicology studies suggest that exposure to these toxicants may adversely impact human health. These findings led to the U.S. Food and Drug Administration’s (FDA) regulation of nicotine-containing E-cigs under the Tobacco Regulation Act (TRA) of 2020. Manufacturers aiming to sell nicotine products in the U.S. must submit a Premarket Tobacco Product Application (PMTA) and obtain FDA approval before marketing their products. However, due to the lengthy PMTA process, some companies have exploited a loophole in the TRA (2020) by introducing nicotine analogs, such as 6-methyl nicotine (6-MN) into E-cig products. 6-MN is marketed as a ‘safer’ alternative to nicotine, offering comparable satisfaction despite not being derived from tobacco or nicotine. Nonetheless, its safety profiles are unknown. Therefore, this study tested the toxicity of 6-MN compared to traditional nicotine <em>in vitro</em>. We observed that thermal degradation of 6-MN in e-liquids significantly generated more ROS in the aerosols than nicotine. We investigated the dose-response cytotoxicity of 6-MN vs nicotine when exposed to HBEC3-KT human bronchial epithelial cells. 6-MN-contained e-liquids significantly increased cytotoxicity and intracellular ROS induction in a dose-specific manner compared to nicotine. Further, we observed that 6-MN (pure compound) transiently increased metabolic activity significantly at all doses tested compared to nicotine. Given the potential risks associated with 6-MN, it cannot be deemed ‘safer’ than nicotine. Therefore, further primary toxicological research is urgently needed to provide regulatory agencies with more robust data to implement regulations.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"405 ","pages":"Pages 9-15"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic activation and hepatic cytotoxicity of osthole mediated by cytochrome P450 enzymes","authors":"Siyu Liu ,&nbsp;Guode Zhao ,&nbsp;Yingyun Xu ,&nbsp;Yang Wang ,&nbsp;Zifang Ding ,&nbsp;Weiwei Li ,&nbsp;Ying Peng ,&nbsp;Jiang Zheng","doi":"10.1016/j.toxlet.2024.12.009","DOIUrl":"10.1016/j.toxlet.2024.12.009","url":null,"abstract":"<div><div>Osthole (OST), a coumarin derivative, is one of the major components of <em>Cnidium monnieri</em> (L.) Cussion. OST was reported to induce apoptosis in hepatocytes. Elevated serum ALT and AST were documented in Sprague-Dawley rats after administration of OST. In the present study, OST was found to be metabolized to a phenol metabolite which was further metabolically oxidized to the corresponding quinone methide intermediate. A glutathione conjugate derived from the reactive metabolite was detected <em>in vitro</em> and <em>in vivo</em>. The structures of the metabolites were verified by chemical analysis. CYP3A4 and CYP1A2 were the major enzymes to catalyze the oxidation reactions. Pre-treatment with 1-aminobenzotriazole or ketoconazole decreased the susceptibility of primary hepatocytes to the cytotoxicity of OST. The findings provided solid evidence that the metabolic activation of OST correlated with the cytotoxicity of OST.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"404 ","pages":"Pages 1-8"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of cell membrane fragments containing muscle type nAChR from Tetronarce californica after preparation using high pressure homogenization","authors":"Fabian Springer ,&nbsp;Marian Freisleben ,&nbsp;Sebastian Muschik ,&nbsp;Franz Worek ,&nbsp;Thomas Seeger ,&nbsp;Lorenz Meinel ,&nbsp;Karin Veronika Niessen","doi":"10.1016/j.toxlet.2024.12.008","DOIUrl":"10.1016/j.toxlet.2024.12.008","url":null,"abstract":"<div><div>The nicotinic acetylcholine receptor (nAChR) is a pentameric ligand-gated ion channel (pLGIC) commonly used as a model for receptors belonging to the Cys-loop superfamily. Members of pLGICs are standardly used in numerous toxicological investigations e.g., GABA and nAChR in the context of nerve agent poisoning. Organophosphorus compounds inhibit AChE, leading to accumulation of acetylcholine in the synaptic cleft and subsequently to a cholinergic crisis, in part through desensitization of nAChR. Due to the limitations of standard therapy, studies concerning functional ligand-receptor interactions of therapeutically active substances are of high importance. Therefore, we developed a novel method to obtain muscle type nAChR-containing membrane fragments from native tissue using high-pressure homogenization. The obtained microsomal fragments were characterized using Dynamic Light Scattering, laser Doppler electrophoresis and protein concentration. The microsomal membrane fragments were further purified, and the plasma membrane fraction was enriched using different density gradients. <em>K</em>_D and <em>B</em>_Max values were determined using a scintillation proximity assay (SPA) with [³H]epibatidine as reporter ligand. Measurement data showed that the ideal conditions to obtain microsomal membrane fragments with high pressure homogenization were four runs at 400 bar. For density gradient centrifugation the under layering of the microsomal membrane fragments (bottom-up method) is to be preferred for further purification. Sucrose seems to be more efficient compared to xylitol or iodixanol density gradients. The nAChR-containing plasma membrane fractions resulting from the developed purification protocol achieve a high degree of quality and reproducibility, making them suitable to model physiological conditions. This system has the potential to be used in both bead- and filtration-based assays probing affinity parameters for ligand binding or functional experiments. The protocol can be easily modified for other LGICs or transmembrane proteins, allowing for further expansion of its use.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"404 ","pages":"Pages 58-66"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the causal effects of perfluorooctanesulfonate on COVID-19 and its associated mechanisms: Integrated Mendelian randomization and network toxicology analyses","authors":"Wenting Tao ,&nbsp;Liang Chen","doi":"10.1016/j.toxlet.2025.01.008","DOIUrl":"10.1016/j.toxlet.2025.01.008","url":null,"abstract":"<div><div>Observational reports have suggested that exposure to perfluorooctanesulfonate (PFOS) can influence COVID-19 infection-related parameters. This study thus sought to use integrated Mendelian randomization (MR) and network toxicology approaches to clarify the potential causal link between PFOS exposure and COVID-19 severity and the molecular mechanisms underlying this relationship. Inverse-variance-weighted analyses highlighted a causal link between plasma PFOS concentrations and a greater risk of sCOVID-19 (<em>OR</em> 1.293<em>, 95 % CI</em> 1.077–1.552, p = 0.006), but not of SARS-CoV-2 infection (p = 0.257) or COVID-19 hospitalization (p = 0.516). No causal link between PFOS concentration and sCOVID-19 was found by reverse MR. In total, 65 targets were tentatively linked to the relationship between PFOS exposure and sCOVID-19. GO and KEGG analyses highlighted involvement in pathways associated with kinase activity, inflammatory responses, and epithelial and endothelial cell migration. In molecular docking analyses, PFOS was confirmed to readily bind to all five analyzed core targets (<em>IL10, ALB, NOTCH1, PPARG,</em> and <em>NFE2L2</em>). These results suggest that PFOS exposure is causally linked to sCOVID-19 risk, while also offering promising insights into the mechanisms that may underlie this association and candidate targets for treatments aimed at limiting the negative effects of PFOS on COVID-19 severity.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"405 ","pages":"Pages 1-8"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of Wnt/β-catenin signaling to increase B lymphoma Moloney murine leukemia virus insertion region 1 by lithium chloride attenuates the toxicity of cisplatin in the HEI-OC1 auditory cells","authors":"Chen Lu ,&nbsp;Chao Chen ,&nbsp;Yingpeng Xu ,&nbsp;Dingyuan Dai ,&nbsp;Chen Sun ,&nbsp;Qi Li","doi":"10.1016/j.toxlet.2024.11.009","DOIUrl":"10.1016/j.toxlet.2024.11.009","url":null,"abstract":"<div><div>Cisplatin is widely used in anti-tumor therapy, but the ototoxicity caused by high-dose cisplatin often limits its efficacy, and the specific mechanism of cisplatin-induced cochlear damage is still not perfect. The Wnt/β-catenin signaling pathway is closely related to aging, embryonic development, and apoptosis. Meanwhile, B lymphoma Moloney murine leukemia virus insertion region 1 (BMI1) plays a certain role in the evolution and development of the inner ear and the occurrence and development of inner ear-related diseases. Our study intends to explore the role and specific mechanism of the Wnt/β-catenin signaling pathway and BMI1 in improving cisplatin ototoxicity. The appropriate experimental concentrations for each drug were selected by CCK-8 cell proliferation assay and Western Blot to detect apoptosis. The lentivirus transfection of HEI-OC1 cochlear hair cells was used to overexpress BMI1. Western Blot, qPCR, and immunofluorescence detected the activation of each component of BMI1 and Wnt/β-catenin signaling pathway in each experimental model. Wnt/β-catenin signaling pathway and BMI1 are jointly involved in cisplatin-induced cell injury. Low lithium chloride (LiCl) concentrations activated the Wnt/β-catenin pathway, increased BMI1 expression, and reduced cisplatin-induced hair cell injury. In contrast, overexpression of BMI1 inhibited the Wnt/β-catenin pathway and reduced hair cell injury. Meanwhile, the increased cisplatin-induced damage to hair cells by inhibiting BMI1 could not be rescued by LiCl. In conclusion, LiCl can ameliorate cisplatin ototoxicity by elevating BMI1 expression through activation of the Wnt/β-catenin pathway. Overexpression of BMI1 inhibits the Wnt/β-catenin pathway and reduces cisplatin-induced hair cell damage.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 50-65"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do Delta-9-tetrahydrocannabinol and Cannabidiol have opposed effects on male fertility?","authors":"Olivia L.M. Scandlan,&nbsp;Laura A. Favetta","doi":"10.1016/j.toxlet.2024.12.003","DOIUrl":"10.1016/j.toxlet.2024.12.003","url":null,"abstract":"<div><div><em>Cannabis sativa</em> is a complex plant, renowned for its diverse array of bioactive compounds, the most prominent of which are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These compounds exhibit markedly opposing pharmacological effects, with THC being primarily psychoactive and CBD known for its non-psychoactive properties. In recent years, there has been growing interest in the potential health implications of these compounds, particularly concerning male reproductive health. Accumulating evidence over the past decade has alluded to the potential negative effects of THC, including its association with reduced sperm quality, altered hormone levels, changes in genetic and epigenetic profiles, and potential impacts on fertility. Conversely, emerging studies suggest that CBD may exert protective and beneficial effects on male reproductive health, possibly through its anti-inflammatory and antioxidant properties. This review aims to provide a comprehensive analysis of the current scientific literature, delineating the mechanisms by which THC and CBD influence male reproductive health, highlighting the disparities in their effects, and discussing the clinical and therapeutic implications of these findings.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 94-104"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the relationship among zinc status, blood manganese levels, and enzymatic markers of tissue damage: an epidemiological study using NHANES 2013-2016 data","authors":"Afnan Alandanoosi ,&nbsp;Florence George ,&nbsp;Juan Liuzzi","doi":"10.1016/j.toxlet.2024.11.011","DOIUrl":"10.1016/j.toxlet.2024.11.011","url":null,"abstract":"<div><div>Manganese is an essential trace element required for various physiological processes. However, excessive exposure to this metal can lead to health issues. This study aims to evaluate whether adequate zinc intake can influence the relationship between blood manganese levels and markers indicating damage to the liver and other organs in populations using epidemiological data. We conducted a comprehensive analysis utilizing 2013–2016 data from the National Health and Nutrition Examination Survey (NHANES). The findings indicated that blood manganese exhibits a significant positive association with the serum levels of enzymatic markers of liver damage alkaline phosphatase and aspartate aminotransferase. However, when investigating the interaction between blood manganese and zinc intake at the second quartile, a significant negative association was found with alkaline phosphatase in three different linear regression models. A similar association was found between the fourth quartile of zinc intake and lactate dehydrogenase activity in all three models of the study. The findings suggest that unhealthy high levels of manganese in populations may lead to tissue injury and disease. Nevertheless, having an adequate zinc intake could help mitigate manganese toxicity.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"403 ","pages":"Pages 76-83"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}