{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:16:37Z","timestamp":1789139797192,"version":"build-2803163510"},"reference-count":86,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973011"],"award-info":[{"award-number":["81973011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Cadmium (Cd) is a highly toxic and pervasive environmental pollutant that exerts detrimental effects on human health through diverse biochemical and molecular mechanisms. As a vital metabolic organ, the liver harbors macrophages that play a crucial role in maintaining hepatic health and function. Current research has paid relatively little attention to the role of macrophages in liver injury induced by heavy metal exposure. This review summarizes current research on the molecular mechanisms underlying cadmium-induced toxicity in hepatic macrophages, focusing on oxidative stress, signaling pathways, gene transcription, and apoptosis. It further examines how cadmium-induced macrophage dysfunction impacts hepatic immunometabolism. Specifically, we detail how cadmium triggers oxidative stress and disrupts intracellular calcium homeostasis, leading to the activation of transcription factors such as NF-\u03baB and Nrf2, and the subsequent engagement of related signaling cascades. These perturbations alter macrophage polarization (M1\/M2), promote cellular damage and apoptosis, and ultimately exacerbate hepatic inflammation and fibrosis. By synthesizing recent advances in this field, this review aims to provide a theoretical foundation and future directions for research, with the goal of informing novel strategies for the prevention and treatment of heavy metal-associated liver diseases.<\/jats:p>","DOI":"10.3390\/toxics14010057","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T14:02:51Z","timestamp":1767794571000},"page":"57","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Research Advances on Cadmium-Induced Toxicity in Hepatic Macrophages"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7447-4128","authenticated-orcid":false,"given":"Jiongfei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of the Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9065-2334","authenticated-orcid":false,"given":"Zhaoan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2252-1963","authenticated-orcid":false,"given":"Wangying","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5275-9383","authenticated-orcid":false,"given":"Shibo","family":"Ying","sequence":"additional","affiliation":[{"name":"School of Public Health, Hangzhou Medical College, Hangzhou 310013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Qu, F., and Zheng, W. (2024). Cadmium Exposure: Mechanisms and Pathways of Toxicity and Implications for Human Health. Toxics, 12.","DOI":"10.3390\/toxics12060388"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00128-020-03088-1","article-title":"A review on Cadmium Exposure in the Population and Intervention Strategies Against Cadmium Toxicity","volume":"106","author":"Wang","year":"2021","journal-title":"Bull. Environ. Contam. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.scitotenv.2019.04.395","article-title":"Cadmium exposure in living organisms: A short review","volume":"678","author":"Zhang","year":"2019","journal-title":"Sci. Total. Environ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"170122","DOI":"10.1183\/16000617.0122-2017","article-title":"Cadmium in tobacco smokers: A neglected link to lung disease?","volume":"27","author":"Ganguly","year":"2018","journal-title":"Eur. Respir. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Smerecza\u0144ski, N.M., and Brz\u00f3ska, M.M. (2023). Current Levels of Environmental Exposure to Cadmium in Industrialized Countries as a Risk Factor for Kidney Damage in the General Population: A Comprehensive Review of Available Data. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098413"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1039\/d0mt00121j","article-title":"Elemental and molecular imaging of human full thickness skin after exposure to heavy metals","volume":"12","author":"Chavatte","year":"2020","journal-title":"Metallomics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e28559","DOI":"10.1097\/MD.0000000000028559","article-title":"Serum cadmium is associated with hepatic steatosis and fibrosis: Korean national health and nutrition examination survey data IV-VII","volume":"101","author":"Han","year":"2022","journal-title":"Medicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"107251","DOI":"10.1016\/j.phrs.2024.107251","article-title":"The association between endocrine disrupting chemicals and nonalcoholic fatty liver disease: A systematic review and meta-analysis","volume":"205","author":"Pan","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"95801","DOI":"10.1007\/s11356-023-29267-1","article-title":"The relationship between cadmium exposure and hepatitis B susceptibility and the establishment of its prediction model","volume":"30","author":"Lu","year":"2023","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"118431","DOI":"10.1016\/j.ecoenv.2025.118431","article-title":"Molecular regulatory networks of microplastics and cadmium mediated hepatotoxicity from NAFLD to tumorigenesis via integrated approaches","volume":"300","author":"Li","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1007\/s11605-013-2210-9","article-title":"Cadmium exposure and liver disease among US adults","volume":"17","author":"Hyder","year":"2013","journal-title":"J. Gastrointest. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s40572-024-00463-6","article-title":"Mechanisms of Metal-Induced Hepatic Inflammation","volume":"11","author":"Subramaniam","year":"2024","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"113163","DOI":"10.1016\/j.ecoenv.2022.113163","article-title":"Association between urine metals and liver function biomarkers in Northeast China: A cross-sectional study","volume":"231","author":"Zhao","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"120300","DOI":"10.1016\/j.lfs.2021.120300","article-title":"Targeting oxidative stress, apoptosis, and autophagy by galangin mitigates cadmium-induced renal damage: Role of SIRT1\/Nrf2 and AMPK\/mTOR pathways","volume":"291","author":"Arab","year":"2022","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s12011-014-0105-6","article-title":"Oxidative stress and Ca2+ signals involved on cadmium-induced apoptosis in rat hepatocyte","volume":"161","author":"Wang","year":"2014","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.1007\/s12011-022-03506-x","article-title":"Alleviative Effect of Threonine on Cadmium-Induced Liver Injury in Mice","volume":"201","author":"Fang","year":"2023","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/jbt.21732","article-title":"Chronic Cadmium Exposure Lead to Inhibition of Serum and Hepatic Alkaline Phosphatase Activity in Wistar Rats","volume":"29","author":"Camacho","year":"2015","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1007\/s00204-003-0499-y","article-title":"Time-course of cadmium-induced acute hepatotoxicity in the rat liver: The role of apoptosis","volume":"77","author":"Tzirogiannis","year":"2003","journal-title":"Arch. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1006\/taap.1999.8833","article-title":"Attenuation of cadmium-induced liver injury in senescent male fischer 344 rats: Role of Kupffer cells and inflammatory cytokines","volume":"162","author":"Yamanoa","year":"2000","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev-immunol-101320-031555","article-title":"Functional Hallmarks of Healthy Macrophage Responses: Their Regulatory Basis and Disease Relevance","volume":"40","author":"Sheu","year":"2022","journal-title":"Annu. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41423-020-00558-8","article-title":"Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities","volume":"18","author":"Wen","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/hep4.1356","article-title":"Liver Macrophages: Old Dogmas and New Insights","volume":"3","author":"Guillot","year":"2019","journal-title":"Hepatol. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ma, X., Qiu, J., Zou, S., Tan, L., and Miao, T. (2024). The role of macrophages in liver fibrosis: Composition, heterogeneity, and therapeutic strategies. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1494250"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1293\/tox.2022-0112","article-title":"Macrophage pathology in hepatotoxicity","volume":"36","author":"Yamate","year":"2023","journal-title":"J. Toxicol. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1080\/09603123.2013.835032","article-title":"Cellular mechanisms of cadmium-induced toxicity: A review","volume":"24","author":"Rani","year":"2014","journal-title":"Int. J. Environ. Health Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102157","DOI":"10.1016\/j.redox.2021.102157","article-title":"Reactive oxygen species trigger NF-\u03baB-mediated NLRP3 inflammasome activation involvement in low-dose CdTe QDs exposure-induced hepatotoxicity","volume":"47","author":"Pang","year":"2021","journal-title":"Redox Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.chemosphere.2019.06.096","article-title":"Exploring the kidney hazard of exposure to mercuric chloride in mice:Disorder of mitochondrial dynamics induces oxidative stress and results in apoptosis","volume":"234","author":"Li","year":"2019","journal-title":"Chemosphere"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"128346","DOI":"10.1016\/j.chemosphere.2020.128346","article-title":"Cadmium induced BEAS-2B cells apoptosis and mitochondria damage via MAPK signaling pathway","volume":"263","author":"Cao","year":"2020","journal-title":"Chemosphere"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jtemb.2011.06.002","article-title":"The toxicity redox mechanisms of cadmium alone or together with copper and zinc homeostasis alteration: Its redox biomarkers","volume":"25","author":"Nzengue","year":"2011","journal-title":"J. Trace Elements Med. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1002\/jat.3788","article-title":"Cell-specific immune-modulation of cadmium on murine macrophages and mast cell lines in vitro","volume":"39","author":"Han","year":"2019","journal-title":"J. Appl. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.fct.2015.02.011","article-title":"Insight into the oxidative stress induced by lead and\/or cadmium in blood, liver and kidneys","volume":"78","author":"Buha","year":"2015","journal-title":"Food Chem. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jtemb.2007.09.024","article-title":"Relation between lipid peroxidation and iron concentration in mouse liver after acute and subacute cadmium intoxication","volume":"22","year":"2008","journal-title":"J. Trace Elements Med. Biol."},{"key":"ref_33","unstructured":"Donatella, C., Antonella, C., Zhichao, C., Angelo, Z., Ciriaco, C., and Serenella, M. (2023). Ferroptosis and Senescence: A Systematic Review. Int. J. Mol. Sci., 24."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.chemosphere.2015.08.084","article-title":"Cadmium exposure to murine macrophages decreases their inflammatory responses and increases their oxidative stress","volume":"144","author":"Jin","year":"2016","journal-title":"Chemosphere"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"111944","DOI":"10.1016\/j.fct.2020.111944","article-title":"Chronic oral exposure to cadmium causes liver inflammation by NLRP3 inflammasome activation in pubertal mice","volume":"148","author":"Li","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1007\/s00204-013-1110-9","article-title":"Cadmium and cellular signaling cascades: Interactions between cell death and survival pathways","volume":"87","author":"Frank","year":"2013","journal-title":"Arch. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/cr.2010.178","article-title":"Crosstalk of reactive oxygen species and NF-\u03baB signaling","volume":"21","author":"Morgan","year":"2011","journal-title":"Cell Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1089\/ars.2010.3534","article-title":"Basic principles and emerging concepts in the redox control of transcription factors","volume":"15","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Davidova, S., Milushev, V., and Satchanska, G. (2024). The Mechanisms of Cadmium Toxicity in Living Organisms. Toxics, 12.","DOI":"10.20944\/preprints202410.1332.v1"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"117263","DOI":"10.1016\/j.taap.2025.117263","article-title":"Nrf2 deficiency aggravates hepatic cadmium accumulation, inflammatory response and subsequent injury induced by chronic cadmium exposure in mice","volume":"497","author":"Chen","year":"2025","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"118100","DOI":"10.1016\/j.ecoenv.2025.118100","article-title":"Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2\/NF-\u03baB signalling pathway","volume":"294","author":"Zhang","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"129043","DOI":"10.1016\/j.jhazmat.2022.129043","article-title":"The role of ferroptosis mediated by NRF2\/ERK-regulated ferritinophagy in CdTe QDs-induced inflammation in macrophage","volume":"436","author":"Liu","year":"2022","journal-title":"J. Hazard. Mater."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"153825","DOI":"10.1016\/j.tox.2024.153825","article-title":"ROS-mediated NRF2\/p-ERK1\/2 signaling-involved mitophagy contributes to macrophages activation induced by CdTe quantum dots","volume":"505","author":"Liu","year":"2024","journal-title":"Toxicology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"105739","DOI":"10.1016\/j.aquatox.2020.105739","article-title":"Cadmium induced oxystress alters Nrf2-Keap1 signaling and triggers apoptosis in piscine head kidney macrophages","volume":"231","author":"Chohelee","year":"2021","journal-title":"Aquat. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"67009","DOI":"10.1289\/EHP13849","article-title":"Prolonged Cadmium Exposure and Osteoclastogenesis: A Mechanistic Mouse and in Vitro Study","volume":"132","author":"Liu","year":"2024","journal-title":"Environ. Health Perspect."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1007\/s00204-016-1661-7","article-title":"Acute exposure to cadmium induces prolonged neutrophilia along with delayed induction of granulocyte colony-stimulating factor in the livers of mice","volume":"90","author":"Horiguchi","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108700","DOI":"10.1016\/j.envres.2019.108700","article-title":"Biological and molecular modifications induced by cadmium and arsenic during breast and prostate cancer development","volume":"178","author":"Vlad","year":"2019","journal-title":"Environ. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.jhep.2024.07.007","article-title":"Infection history imprints prolonged changes to the epigenome, transcriptome and function of Kupffer cells","volume":"81","author":"Benoit","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_49","first-page":"15","article-title":"The critical role of autophagy in cadmium-induced immunosuppression regulated by endoplasmic reticulum stress-mediated calpain activation in RAW264.7 mouse monocytes","volume":"393","year":"2017","journal-title":"Toxicology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0898-6568(01)00268-6","article-title":"Cadmium-induced DNA synthesis and cell proliferation in macrophages: The role of intracellular calcium and signal transduction mechanisms","volume":"14","author":"Misra","year":"2002","journal-title":"Cell. Signal."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1091\/mbc.e08-07-0762","article-title":"Role of the tumor suppressor PTEN in antioxidant responsive element-mediated transcription and associated histone modifications","volume":"20","author":"Sakamoto","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1093\/toxsci\/kfu013","article-title":"Cadmium selectively induces MIP-2 and COX-2 through PTEN-mediated Akt activation in RAW264.7 cells","volume":"138","author":"Huang","year":"2014","journal-title":"Toxicol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"113015","DOI":"10.1016\/j.ecoenv.2021.113015","article-title":"Cadmium exposure activates the PI3K\/AKT signaling pathway through miRNA-21, induces an increase in M1 polarization of macrophages, and leads to fibrosis of pig liver tissue","volume":"228","author":"Cui","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1021\/acs.jafc.2c06562","article-title":"Nano-Selenium Antagonized Cadmium-Induced Liver Fibrosis in Chicken","volume":"71","author":"Sun","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/toxsci\/kfh221","article-title":"Calcium-mediated activation of c-Jun NH2-terminal kinase (JNK) and apoptosis in response to cadmium in murine macrophages","volume":"81","author":"Kim","year":"2004","journal-title":"Toxicol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"152899","DOI":"10.1016\/j.tox.2021.152899","article-title":"Subacute cadmium exposure promotes M1 macrophage polarization through oxidative stress-evoked inflammatory response and induces porcine adrenal fibrosis","volume":"461","author":"Yao","year":"2021","journal-title":"Toxicology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6411","DOI":"10.7150\/ijbs.115073","article-title":"Glycolysis drives STING signaling to promote M1-macrophage polarization and aggravate liver fibrosis","volume":"21","author":"Chen","year":"2025","journal-title":"Int. J. Biol. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Lu, Q., Ong, M., Yi, X., Xing, M., Tian, X., Zhang, K., Lu, L., Wang, H., Lin, X., and Fang, J. (2025). F13A1-Mediated Macrophage Activation Promotes MASH Progression via the PKM2\/HIF1A Pathway. Adv. Sci., e18128.","DOI":"10.1002\/advs.202518128"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15754","DOI":"10.1074\/jbc.RA120.013632","article-title":"Cadmium-mediated lung injury is exacerbated by the persistence of classically activated macrophages","volume":"295","author":"Gu","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s12011-017-1071-6","article-title":"Cadmium Alters the Concentration of Fatty Acids in THP-1 Macrophages","volume":"182","author":"Olszowski","year":"2018","journal-title":"Biol. Trace Element Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Dumkova, J., Vrlikova, L., Vecera, Z., Putnova, B., Docekal, B., Mikuska, P., Fictum, P., Hampl, A., and Buchtova, M. (2016). Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060874"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-pathmechdis-012418-012718","article-title":"Diversity, Mechanisms, and Significance of Macrophage Plasticity","volume":"15","author":"Locati","year":"2020","journal-title":"Annu. Rev. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1002\/jcp.26429","article-title":"Macrophage plasticity, polarization, and function in health and disease","volume":"233","author":"Mohammadian","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3390\/livers4030033","article-title":"Understanding Macrophage Complexity in Metabolic Dysfunction-Associated Steatotic Liver Disease: Transitioning from the M1\/M2 Paradigm to Spatial Dynamics","volume":"4","author":"Ahamed","year":"2024","journal-title":"Livers"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.livres.2022.11.001","article-title":"Hepatic transcriptome profiling reveals early signatures associated with disease transition from non-alcoholic steatosis to steatohepatitis","volume":"6","author":"Magee","year":"2022","journal-title":"Liver Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1002\/tox.23641","article-title":"Molybdenum and cadmium co-exposure promotes M1 macrophage polarization through oxidative stress-mediated inflammatory response and induces pulmonary fibrosis in Shaoxing ducks (Anas platyrhyncha)","volume":"37","author":"Huang","year":"2022","journal-title":"Environ. Toxicol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.toxrep.2022.01.009","article-title":"Cadmium and wild boar: Environmental exposure and immunological impact on macrophages","volume":"9","author":"Franzoni","year":"2022","journal-title":"Toxicol. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1248\/bpb.b212014","article-title":"Cadmium renal toxicity via apoptotic pathways","volume":"35","author":"Yasuyuki","year":"2012","journal-title":"Biol. Pharm. Bull."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"44380","DOI":"10.1074\/jbc.M111.257519","article-title":"Autophagy induced by deficiency of sphingosine-1-phosphate phosphohydrolase 1 is switched to apoptosis by calpain-mediated autophagy-related gene 5 (Atg5) cleavage","volume":"286","author":"Allegood","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1055\/s-0038-1670674","article-title":"Regulation of Hepatic Inflammation via Macrophage Cell Death","volume":"38","author":"Li","year":"2018","journal-title":"Semin. Liver Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"102353","DOI":"10.1007\/s11356-023-29424-6","article-title":"Burden of diabetes attributable to dietary cadmium exposure in adolescents and adults in China","volume":"30","author":"Li","year":"2023","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1053\/j.gastro.2019.11.311","article-title":"Mechanisms of Fibrosis Development in Nonalcoholic Steatohepatitis","volume":"158","author":"Schwabe","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s11658-023-00498-x","article-title":"Cadmium promotes nonalcoholic fatty liver disease by inhibiting intercellular mitochondrial transfer","volume":"28","author":"Sun","year":"2023","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1515\/intox-2015-0023","article-title":"Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats","volume":"8","author":"Samarghandian","year":"2015","journal-title":"Interdiscip. Toxicol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"113306","DOI":"10.1016\/j.ecoenv.2022.113306","article-title":"Chronic exposure to low-dose cadmium facilitated nonalcoholic steatohepatitis in mice by suppressing fatty acid desaturation","volume":"233","author":"Zhu","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"115040","DOI":"10.1016\/j.ecoenv.2023.115040","article-title":"Saturated fatty acids synergizes cadmium to induce macrophages M1 polarization and hepatic inflammation","volume":"259","author":"Zhu","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Lee, J.-Y., Tokumoto, M., and Satoh, M. (2025). Molecular Mechanisms of Cadmium-Induced Toxicity and Its Modification. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157515"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41401-020-0396-4","article-title":"Zinc as a countermeasure for cadmium toxicity","volume":"42","author":"Yu","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Tokumoto, M., Lee, J.-Y., Fujiwara, Y., and Satoh, M. (2023). Long-Term Exposure to Cadmium Causes Hepatic Iron Deficiency through the Suppression of Iron-Transport-Related Gene Expression in the Proximal Duodenum. Toxics, 11.","DOI":"10.3390\/toxics11070641"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.toxlet.2020.07.005","article-title":"Cadmium induces iron deficiency anemia through the suppression of iron transport in the duodenum","volume":"332","author":"Fujiwara","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e22440","DOI":"10.1002\/jbt.22440","article-title":"Vitamin D(3) and calcium cosupplementation alleviates cadmium hepatotoxicity in the rat: Enhanced antioxidative and anti-inflammatory actions by remodeling cellular calcium pathways","volume":"34","author":"Refaat","year":"2020","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"111610","DOI":"10.1016\/j.ecoenv.2020.111610","article-title":"Vitamin E protects against cadmium-induced sub-chronic liver injury associated with the inhibition of oxidative stress and activation of Nrf2 pathway","volume":"208","author":"Fang","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"155337","DOI":"10.1016\/j.phymed.2024.155337","article-title":"Baicalin and N-acetylcysteine regulate choline metabolism via TFAM to attenuate cadmium-induced liver fibrosis","volume":"125","author":"Sun","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"159589","DOI":"10.1016\/j.bbalip.2024.159589","article-title":"Effect of glucose selenol on hepatic lipid metabolism disorder induced by heavy metal cadmium in male rats","volume":"1870","author":"Yang","year":"2025","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/hep.30249","article-title":"Pharmacological Inhibition of CCR2\/5 Signaling Prevents and Reverses Alcohol-Induced Liver Damage, Steatosis, and Inflammation in Mice","volume":"69","author":"Ambade","year":"2019","journal-title":"Hepatology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1002\/hep.29544","article-title":"Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis","volume":"67","author":"Krenkel","year":"2018","journal-title":"Hepatology"}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/1\/57\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T05:29:22Z","timestamp":1767936562000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/1\/57"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":86,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["toxics14010057"],"URL":"https:\/\/doi.org\/10.3390\/toxics14010057","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]}}}