{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T03:27:50Z","timestamp":1777778870878,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T00:00:00Z","timestamp":1685145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institutional Fund Projects","award":["IFPIP: 446-141-1443"],"award-info":[{"award-number":["IFPIP: 446-141-1443"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>In this study, cobalt neurotoxicity was investigated in human astrocytoma and neuroblastoma (SH-SY5Y) cells using proliferation assays coupled with LC\u2013MS-based metabolomics and transcriptomics techniques. Cells were treated with a range of cobalt concentrations between 0 and 200 \u00b5M. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed cobalt cytotoxicity and decreased cell metabolism in a dose and time-dependent manner was observed by metabolomics analysis, in both cell lines. Metabolomic analysis also revealed several altered metabolites particularly those related to DNA deamination and methylation pathways. One of the increased metabolites was uracil which can be generated from DNA deamination or fragmentation of RNA. To investigate the origin of uracil, genomic DNA was isolated and analyzed by LC\u2013MS. Interestingly, the source of uracil, which is uridine, increased significantly in the DNA of both cell lines. Additionally, the results of the qRT-PCR showed an increase in the expression of five genes Mlh1, Sirt2, MeCP2, UNG, and TDG in both cell lines. These genes are related to DNA strand breakage, hypoxia, methylation, and base excision repair. Overall, metabolomic analysis helped reveal the changes induced by cobalt in human neuronal-derived cell lines. These findings could unravel the effect of cobalt on the human brain.<\/jats:p>","DOI":"10.3390\/metabo13060698","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T16:18:43Z","timestamp":1685204323000},"page":"698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Metabolomics Analysis as a Tool to Measure Cobalt Neurotoxicity: An In Vitro Validation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4865-7215","authenticated-orcid":false,"given":"Ibrahim M.","family":"Alanazi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7782-0574","authenticated-orcid":false,"given":"Abdullah","family":"R. Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2855-5134","authenticated-orcid":false,"given":"Torki A.","family":"Zughaibi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4488-2194","authenticated-orcid":false,"given":"Ahmed I.","family":"Al-Asmari","sequence":"additional","affiliation":[{"name":"Laboratory Department, King Abdul-Aziz Hospital, Ministry of Health, Jeddah 22421, Saudi Arabia"},{"name":"Toxicology and Forensic Science Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-415X","authenticated-orcid":false,"given":"Shams","family":"Tabrez","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Strathclyde, Glasgow G4 0NW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1094-7604","authenticated-orcid":false,"given":"David","family":"Watson","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Helen","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Strathclyde, Glasgow G4 0NW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14551","DOI":"10.1073\/pnas.0805989105","article-title":"Decyanation of vitamin B12 by a trafficking chaperone","volume":"105","author":"Kim","year":"2008","journal-title":"Proc. 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