{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:49:37Z","timestamp":1783655377887,"version":"3.55.0"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cadmium (Cd), a prevalent environmental toxin and pollutant capable of causing neurodegenerative diseases (NDs) like Alzheimer's and Parkinson's, primarily through oxidative stress, calcium imbalance, and neuroinflammation\u2010induced mechanisms. Cd exposure increases the level of reactive oxygen species (ROS) and disrupts neurotransmitters by lowering antioxidants, leading to neuron death. Cd exposure in zebrafish results in neurodegeneration, with motor, mental, and behavioral impairments. The efficacy of the DOPA\u201031 intervention at varying concentrations was evaluated through the behavioral tests, biochemical assays for antioxidant enzyme activities (SOD, CAT, GSH, MDA), and histopathological analysis. Additionally, the alterations in expression levels of inflammation (\n                    <jats:italic>tnf\u2010\u03b1, il\u20101\u03b2<\/jats:italic>\n                    ) and neuroprotective (\n                    <jats:italic>bdnf, syn2a<\/jats:italic>\n                    ) genes were also assessed. The Cd exposure exhibited the major deficits in the key behavioral parameters (motor, anxiety, and cognitive impairment). It disrupted antioxidant enzyme activity, increased lipid peroxidation, and elevated acetyl cholinesterase (AChE) activity, leading to cholinergic dysfunction. Histopathology showed extensive neuronal damage and amyloid\u2010like protein aggregation. DOPA\u201031 at a 20\u2009\u00b5M concentration, substantially exhibited antioxidant and AChE activity by reducing oxidative stress and improving motor and cognitive functions. Molecular analysis of DOPA\u201031 treatment showed significant downregulation of pro\u2010inflammatory markers and upregulation of neuroprotective factors. In addition, DOPA\u201031 restored behavioral changes by potentially mitigating neuronal damage and protein aggregation caused by the Cd\u2010induced neurotoxicity. This research investigation suggests the novel drug candidate DOPA\u201031 as a preliminary treatment for Neurodegenerative Disorder (NDD)\u2010like features and warrants further exploration in higher animal models to assess clinical relevance.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70872","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:17:22Z","timestamp":1777461442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Combating Cadmium\u2010Induced Neurotoxicity, Oxidative Stress, and Inflammatory Pathways Using DOPA\u201031, a Dioxopiperidinamide Derivative in an In Vivo Zebrafish Model"],"prefix":"10.1002","volume":"40","author":[{"given":"Santhanam Sanjai","family":"Dharshan","sequence":"first","affiliation":[{"name":"Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities SRM Institute of Science and Technology, Kattankulatur Chengalpattu District Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Madesh","sequence":"additional","affiliation":[{"name":"Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities SRM Institute of Science and Technology, Kattankulatur Chengalpattu District Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthikeyan","family":"Ramamurthy","sequence":"additional","affiliation":[{"name":"Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities SRM Institute of Science and Technology, Kattankulatur Chengalpattu District Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeyalakshmi","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur Chengalpattu District Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaliraj","family":"Salamuthu","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur Chengalpattu District Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhlid H.","family":"Almutairi","sequence":"additional","affiliation":[{"name":"Department of Zoology College of Science, King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bader O.","family":"Almutairi","sequence":"additional","affiliation":[{"name":"Department of Zoology College of Science, King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2894-1905","authenticated-orcid":false,"given":"S. Karthick Raja","family":"Namasivayam","sequence":"additional","affiliation":[{"name":"Centre for Applied Research, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS) Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathiravan Muthu","family":"Kumaradoss","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, SRM College of Pharmacy, Faculty of Medicine and Health Sciences SRM Institute of Science and Technology, Kattankulathur Chengalpattu District Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesu","family":"Arockiaraj","sequence":"additional","affiliation":[{"name":"Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities SRM Institute of Science and Technology, Kattankulatur Chengalpattu District Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"issue":"7","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a028035","article-title":"Pathology of Neurodegenerative Diseases","volume":"9","author":"Dugger B. 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