{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:27:25Z","timestamp":1793161645307,"version":"4.5.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u00a0<\/jats:title>\n                  <jats:p>Erythropoietin (EPO) is known for its role in hematopoiesis and also exhibits anti-inflammatory, anti-apoptotic, antioxidant, and cytoprotective properties. However, its clinical application is limited by hematopoietic side effects. ARA290, a non-hematopoietic derivative of EPO, selectively activates the innate repair receptor (IRR) and replicates these protective effects without the associated hematopoietic complications. Cadmium (Cd), a prevalent environmental toxin, causes neurotoxic damage through mechanisms such as oxidative stress, genotoxicity, apoptosis, and inflammation. This study explored ARA290\u2019s neuroprotective effects against cadmium-induced toxicity in PC12 cells, an in vitro model for neuronal health. PC12 cells pretreated with ARA290 showed significantly improved cell viability in the MTT assay, indicating reduced cytotoxicity. The comet assay revealed decreased DNA damage, suggesting reduced genotoxicity. ARA290 also alleviated oxidative stress, as evidenced by reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), alongside increased glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD) activities. A marker of apoptosis, TUNEL-positive cells, was significantly reduced. Additionally, ARA290 decreased inflammatory markers such as TNF alpha, IL1\u00df and IL 6. These findings demonstrate that ARA290, via IRR activation, provides robust neuroprotection against cadmium-induced toxicity, suggesting a multi-faceted protective mechanism. This highlights ARA290\u2019s potential therapeutic role in managing heavy metal-induced neurotoxicity and supports further research into its long-term effects and applications in other neurodegenerative diseases or conditions involving environmental toxins.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n               <\/jats:sec>","DOI":"10.1093\/toxres\/tfaf023","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T08:35:01Z","timestamp":1739781301000},"source":"Crossref","is-referenced-by-count":15,"title":["Mechanisms of ARA290 in counteracting cadmium-triggered neurotoxicity in PC12 cells"],"prefix":"10.1093","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5756-7575","authenticated-orcid":false,"given":"Farzaneh","family":"Motafeghi","sequence":"first","affiliation":[{"name":"Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tajrish, Taleqani St, No. 24, P.O. Box 19395-4763, Tehran ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam S","family":"Fakhri B","sequence":"additional","affiliation":[{"name":"Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences , District 6, Pour Sina St, P94+V8MF, Tehran Province, Tehran ,","place":["Iran"]},{"name":"Department of Internal Medicine, School of Medicine, Tehran University of Medical Science, (TUMS) , District 6, Pour Sina St, P94V+8MF, Tehran Province, Tehran ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-4262","authenticated-orcid":false,"given":"Nasrin","family":"Ghassemi Barghi","sequence":"additional","affiliation":[{"name":"Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences , District 6, Pour Sina St, P94+V8MF, Tehran Province, Tehran 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