{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:36:33Z","timestamp":1788489393407,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bortezomib (BTZ) is a commonly used antitumor drug, but its peripheral neuropathy side effect poses a limitation on its dosage. Evodiamine (EVO) exhibits various biological activities, including antioxidant, anti\u2010inflammatory, and anticancer effects. The purpose of this investigation is to confirm the impact of EVO on BTZ\u2010induced peripheral neurotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>GeneCards and HERB were applied to analyze the targets of peripheral neurotoxicity and EVO. The Gene Ontology (GO)\u00a0and Kyoto Encyclopedia of Genes and Genomes (KEGG)\u00a0pathways enrichment analysis of the hub genes were identified by DAVID. Rat dorsal root ganglion neurons (DRGs) and rat RSC96 Schwann cells (SCs) were treated with BTZ to simulate peripheral neurotoxicity. BTZ\u2010induced peripheral neurotoxicity was assessed by detecting cell viability, proliferation, oxidative stress, and ferroptosis in DRGs and SCs. The mitogen\u2010activated protein kinase (MAPK) signaling was scrutinized by Western blot assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The Venn diagram for the overlapping targets of EVO and peripheral neurotoxicity showed that EVO might regulate peripheral neurotoxicity by influencing cell oxidative stress, ferroptosis, and MAPK signaling pathway. EVO attenuated BTZ\u2010induced toxicity in DRGs and SCs. EVO attenuated BTZ\u2010induced oxidative stress damage in DRGs and SCs by reducing reactive oxygen species and malondialdehyde levels and enhancing glutathione level. EVO attenuated BTZ\u2010induced ferroptosis in DRGs and SCs. EVO inhibited BTZ\u2010induced activation of the MAPK signaling in DRGs and SCs. Activation of the MAPK signaling reversed the neuroprotective effect of EVO on BTZ\u2010induced oxidative stress injury and ferroptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>EVO attenuated oxidative stress and ferroptosis by inhibiting the MAPK signaling to improve BTZ\u2010induced peripheral neurotoxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/tox.24035","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T20:12:08Z","timestamp":1701115928000},"page":"1556-1566","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Evodiamine attenuates oxidative stress and ferroptosis by inhibiting the\n                    <scp>MAPK<\/scp>\n                    signaling to improve bortezomib\u2010induced peripheral neurotoxicity"],"prefix":"10.1002","volume":"39","author":[{"given":"Yunlong","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Hematology Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital  Yancheng Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiying","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Hematology The Third Affiliated Hospital of Soochow University  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8919-3554","authenticated-orcid":false,"given":"Lingling","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Oncology Yancheng Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine  Yancheng Jiangsu 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