{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:58:01Z","timestamp":1786978681734,"version":"build-2736575974"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Many studies have focused on the neurotoxic effects of single metals, while investigation on the exposure to metal mixtures, which mainly occur in real\u2010life situations, is scarce. This study sought to assess the neurotoxic effect of Ni, Co, and Pb binary mixtures and their individual effects in hippocampal neuronal cells (HT\u201022). Cells were exposed to Ni, Co, and Pb separately for 48\u2009h at 37\u00b0C and 5% CO\n                    <jats:sub>2<\/jats:sub>\n                    , and cell viability was assessed. Morphological assessment of the cells exposed to binary mixtures of Co, Ni, and Pb and single metals was assessed using a microscope. Furthermore, acetylcholinesterase (AChE) activity, oxidative stress biomarkers (glutathione [GSH] and malondialdehyde [MDA] levels, catalase [CAT], and glutathione\u2010S transferase [GST] activities) and nitric oxide [NO] levels were evaluated after treatment with the binary mixtures and single metals. Binary mixtures of the metals reduced cell viability, exerting an additivity action. The combinations also exerted synergistic action, as revealed by the combination index. Furthermore, a significant reduction in AChE activity, GSH levels, CAT and GST activities, and high MDA and NO levels were observed in neuronal cells. The additive interactions and synergistic actions of the binary mixtures might contribute to the significant reduction of AChE activity, GSH levels, GST, and CAT activities, and an increase in MDA and NO levels. The findings from this study revealed significant evidence that binary mixtures of Co, Pb, and Ni may induce impaired neuronal function and, ultimately, neurodegeneration.\n                  <\/jats:p>","DOI":"10.1002\/tox.24418","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T08:49:41Z","timestamp":1728031781000},"page":"128-139","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Assessment of Neurotoxic Mechanisms of Individual and Binary Mixtures of Cobalt, Nickel and Lead in Hippocampal Neuronal Cells"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0379-3838","authenticated-orcid":false,"given":"Tosin A.","family":"Olasehinde","sequence":"first","affiliation":[{"name":"Nutrition and Toxicology Division, Food Technology Department Federal Institute of Industrial Research  Lagos Nigeria"},{"name":"Discipline of Microbiology, School of Life Sciences University of Kwazulu\u2010Natal  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ademola O.","family":"Olaniran","sequence":"additional","affiliation":[{"name":"Discipline of Microbiology, School of Life Sciences University of Kwazulu\u2010Natal  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jksus.2022.101865"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R116.749259"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e04691"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7643-8340-4_6"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2018.01.007"},{"issue":"20","key":"e_1_2_10_7_1","article-title":"Determination of the Heavy Metal Bioaccumulation Patterns in Muscles of Two Species of Mullets From the Southern Caspian Sea","volume":"12","author":"Bakhshalizadeh S.","year":"2022","journal-title":"Animals (Basel)"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111257"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2017.10.002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.643972"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/EE9.0000000000000192"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2021.126378"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867325666171129124616"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2022.159432"},{"issue":"12","key":"e_1_2_10_15_1","article-title":"Association Between Heavy Metal Exposure and Parkinson's Disease: A Review of the Mechanisms Related to Oxidative Stress","volume":"11","author":"Pyatha S.","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2021.09.004"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jenvman.2019.05.145"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxics10020059"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2019.03.003"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ant.2020.11.002"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2017.10.006"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2021.1917382"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-015-0267-x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfj073"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(02)00036-7"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(61)90145-9"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(84)05016-3"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90090-6"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)42083-8"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/s30800276"},{"issue":"2","key":"e_1_2_10_31_1","first-page":"188","article-title":"Lipid Peroxidation in Rat Brain Is Increased by Simulated Weightlessness and Decreased by a Soy\u2010Protein Diet","volume":"32","author":"Chowdhury P.","year":"2002","journal-title":"Annals of Clinical and Laboratory Science"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxics9090198"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-016-6333-x"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-014-9791-y"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2007.05.003"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2017-0228"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-019-00469-2"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy132"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.08.036"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118826"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/321213"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/13547500500264660"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/321213"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.marenvres.2012.11.005"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9080647"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147432"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.2174\/157015909787602823"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24081583"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2007.00329.x"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2234"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.2174\/18756190MTA2pMjApy"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12291-014-0446-0"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20102407"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00029.2006"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370221997052"},{"issue":"10","key":"e_1_2_10_56_1","article-title":"Inhibition of Neuroinflammatory Nitric Oxide Signaling Suppresses Glycation and Prevents Neuronal Dysfunction in Mouse Prion Disease","volume":"118","author":"Bourgognon J. M.","year":"2021","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.07.001"}],"container-title":["Environmental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.24418","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:12:03Z","timestamp":1733789523000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tox.24418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,4]]},"references-count":56,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/tox.24418"],"URL":"https:\/\/doi.org\/10.1002\/tox.24418","archive":["Portico"],"relation":{},"ISSN":["1520-4081","1522-7278"],"issn-type":[{"value":"1520-4081","type":"print"},{"value":"1522-7278","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,4]]},"assertion":[{"value":"2023-06-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}