{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:45:11Z","timestamp":1788529511658,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundations of China","award":["U1812403"],"award-info":[{"award-number":["U1812403"]}]},{"name":"Natural Science Foundations of China","award":["81872569"],"award-info":[{"award-number":["81872569"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Compelling evidence has demonstrated that arsenic (As) exposure is associated with kidney injuries. Given that inflammatory responses and immune imbalances are the root causes of several kidney diseases, this study investigated the potential mechanisms underlying NLRP3 inflammasome activation in As-induced kidney injury. A rat model of sub-chronic As exposure was established via oral administration of NaAsO2. The results revealed that urinary \u03b2-2-microglobulin (\u03b22-MG), N-acetyl-\u03b2-D-glucosidase (NAG) and albumin (ALB) were increased in the As-exposed group, reflecting kidney impairment. Moreover, significant glomerular vacuole-like changes, tubular dilatation and inflammatory cell infiltration were observed. Meanwhile, the expression levels of neutrophil gelatinase-associated lipocalin (NGAL), IL-1\u03b2 and IL-18 were enhanced in the kidney tissues of As-treated rats. Further, increased expression of NLRP3, ASC and caspase-1, which are NLRP3 inflammasome-associated proteins, were observed in the kidney tissues of rats in the As-treated groups. The expression levels of the NLRP3 upstream regulators C\/EBP\u03b2 and TFAM were also elevated. These findings suggest that sub-chronic As exposure triggers inflammatory responses in rat kidney tissue and impairs kidney function. The underlying mechanisms may be related to the C\/EBP\u03b2\u2013TFAM pathway and activation of the NLRP3 inflammasome pathway.<\/jats:p>","DOI":"10.3390\/toxics11080668","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T11:17:17Z","timestamp":1690975037000},"page":"668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["C\/EBP\u03b2\u2013TFAM-Mediated NLRP3 Inflammasome Activation Contributes to Arsenic-Induced Rat Kidney Injury"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7696-6004","authenticated-orcid":false,"given":"Ziqin","family":"Wu","sequence":"first","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Wang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daopeng","family":"Luo","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, China"},{"name":"Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-Constructed by the Province and Ministry, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1126\/science.aba1510","article-title":"Global threat of arsenic in groundwater","volume":"368","author":"Podgorski","year":"2020","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117940","DOI":"10.1016\/j.envpol.2021.117940","article-title":"Environmental arsenic exposure and its contribution to human diseases, toxicity mechanism and management","volume":"289","author":"Rahaman","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.jhazmat.2016.09.032","article-title":"Associations between arsenic in drinking water and the progression of chronic kidney disease: A nationwide study in Taiwan","volume":"321","author":"Cheng","year":"2017","journal-title":"J. Hazard. Mater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"152800","DOI":"10.1016\/j.tox.2021.152800","article-title":"Arsenic methylation\u2013Lessons from three decades of research","volume":"457","author":"Thomas","year":"2021","journal-title":"Toxicology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1039\/C5TX00165J","article-title":"A possible new mechanism and drug intervention for kidney damage due to arsenic poisoning in rats","volume":"5","author":"Xu","year":"2016","journal-title":"Toxicol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.taap.2003.10.022","article-title":"Chronic health effects in people exposed to arsenic via the drinking water: Dose-response relationships in review","volume":"198","author":"Yoshida","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1053\/j.ajkd.2012.09.011","article-title":"Urine arsenic and prevalent albuminuria: Evidence from a population-based study","volume":"61","author":"Zheng","year":"2013","journal-title":"Am. J. Kidney Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1021\/acs.jafc.7b05746","article-title":"Arsenic Speciation and Accumulation in Selected Organs after Oral Administration of Rice Extracts in Wistar Rats","volume":"66","author":"Lewchalermvong","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1080\/15548627.2017.1309485","article-title":"Autophagy and kidney inflammation","volume":"13","author":"Kimura","year":"2017","journal-title":"Autophagy"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Fusco, R., Siracusa, R., Genovese, T., Cuzzocrea, S., and Di Paola, R. (2020). Focus on the Role of NLRP3 Inflammasome in Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124223"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nrc704","article-title":"Hypoxia\u2013A key regulatory factor in tumour growth","volume":"2","author":"Harris","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/imr.12296","article-title":"Regulation of inflammasome activation","volume":"265","author":"Man","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41419-023-05587-5","article-title":"HIF1alpha-BNIP3-mediated mitophagy protects against renal fibrosis by decreasing ROS and inhibiting activation of the NLRP3 inflammasome","volume":"14","author":"Li","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.7150\/thno.50905","article-title":"Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance","volume":"11","author":"Zhao","year":"2021","journal-title":"Theranostics"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, Q., Ma, L., Sun, B., and Zhang, A. (2023). Reduced Peripheral Blood Mitochondrial DNA Copy Number as Identification Biomarker of Suspected Arsenic-Induced Liver Damage. Biol. Trace. Elem. Res., ahead of print.","DOI":"10.1007\/s12011-023-03584-5"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"114208","DOI":"10.1016\/j.ecoenv.2022.114208","article-title":"Association and risk of circulating inflammatory markers with hyperglycemia in coal-burning arsenicosis","volume":"247","author":"Liu","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.mcn.2018.04.005","article-title":"Pattern recognition receptors mediate pro-inflammatory effects of extracellular mitochondrial transcription factor A (TFAM)","volume":"89","author":"Schindler","year":"2018","journal-title":"Mol. Cell Neurosci."},{"key":"ref_19","first-page":"199","article-title":"Mitochondrial transcription factor A is a proinflammatory mediator in hemorrhagic shock","volume":"30","author":"Chaung","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nature23890","article-title":"cGAS senses long and HMGB\/TFAM-bound U-turn DNA by forming protein-DNA ladders","volume":"549","author":"Andreeva","year":"2017","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.gene.2007.07.011","article-title":"Transcription factor hStaf\/ZNF143 is required for expression of the human TFAM gene","volume":"401","author":"Gerard","year":"2007","journal-title":"Gene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"563","DOI":"10.4049\/jimmunol.182.1.563","article-title":"Inflammatory cytokine production by human neutrophils involves C\/EBP transcription factors","volume":"182","author":"Cloutier","year":"2009","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115757","DOI":"10.1016\/j.taap.2021.115757","article-title":"Arsenic-induced lung inflammation and fibrosis in a rat model: Contribution of the HMGB1\/RAGE, PI3K\/AKT, and TGF-beta1\/SMAD pathways","volume":"432","author":"Wang","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1289\/ehp.1205875","article-title":"The broad scope of health effects from chronic arsenic exposure: Update on a worldwide public health problem","volume":"121","author":"Naujokas","year":"2013","journal-title":"Environ. Health Perspect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/tox.22291","article-title":"RKIP expression of liver and kidney after arsenic exposure","volume":"32","author":"Tsao","year":"2017","journal-title":"Environ. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8414047","DOI":"10.1155\/2022\/8414047","article-title":"Arsenic Induces Continuous Inflammation and Regulates Th1\/Th2\/Th17\/Treg Balance in Liver and Kidney In Vivo","volume":"2022","author":"Duan","year":"2022","journal-title":"Mediat. Inflamm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"52655","DOI":"10.1007\/s11356-022-19521-3","article-title":"Sex-specific differences in early renal impairment associated with arsenic, lead, and cadmium exposure among young adults in Taiwan","volume":"29","author":"Liao","year":"2022","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.kint.2022.03.029","article-title":"Susceptibility to kidney fibrosis in mice is associated with early growth response-2 protein and tissue inhibitor of metalloproteinase-1 expression","volume":"102","author":"Kokeny","year":"2022","journal-title":"Kidney Int."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rysz, J., Gluba-Brzozka, A., Franczyk, B., Jablonowski, Z., and Cialkowska-Rysz, A. (2017). Novel Biomarkers in the Diagnosis of Chronic Kidney Disease and the Prediction of Its Outcome. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081702"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s00134-018-5126-8","article-title":"Biomarkers for prediction of renal replacement therapy in acute kidney injury: A systematic review and meta-analysis","volume":"44","author":"Klein","year":"2018","journal-title":"Intensive Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1002\/tox.23324","article-title":"Imbalanced inflammatory response in subchronic arsenic-induced liver injury and the protective effects of Ginkgo biloba extract in rats: Potential role of cytokines mediated cell-cell interactions","volume":"36","author":"Dong","year":"2021","journal-title":"Environ. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.kint.2019.01.014","article-title":"Multifactorial functions of the inflammasome component NLRP3 in pathogenesis of chronic kidney diseases","volume":"96","author":"Mulay","year":"2019","journal-title":"Kidney Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.bbrc.2019.12.022","article-title":"Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux","volume":"523","author":"Rodrigues","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/s41581-019-0234-4","article-title":"Innate immunity in diabetic kidney disease","volume":"16","author":"Tang","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kaminski, T.W., Pawlak, K., Karbowska, M., Mysliwiec, M., and Pawlak, D. (2017). Indoxyl sulfate\u2013The uremic toxin linking hemostatic system disturbances with the prevalence of cardiovascular disease in patients with chronic kidney disease. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0457-1"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3497","DOI":"10.1007\/s00204-021-03157-2","article-title":"Cadmium induces renal inflammation by activating the NLRP3 inflammasome through ROS\/MAPK\/NF-kappaB pathway in vitro and in vivo","volume":"95","author":"Li","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"714340","DOI":"10.3389\/fimmu.2021.714340","article-title":"NLRP3 Inflammasome in Metabolic-Associated Kidney Diseases: An Update","volume":"12","author":"Xiong","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kim, Y.G., Kim, S.M., Kim, K.P., Lee, S.H., and Moon, J.Y. (2019). The Role of Inflammasome-Dependent and Inflammasome-Independent NLRP3 in the Kidney. Cells, 8.","DOI":"10.3390\/cells8111389"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.molimm.2020.08.023","article-title":"The interaction between C\/EBPbeta and TFAM promotes acute kidney injury via regulating NLRP3 inflammasome-mediated pyroptosis","volume":"127","author":"Dai","year":"2020","journal-title":"Mol. Immunol."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/11\/8\/668\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:24:41Z","timestamp":1760127881000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/11\/8\/668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,2]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["toxics11080668"],"URL":"https:\/\/doi.org\/10.3390\/toxics11080668","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,2]]}}}