{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:55:16Z","timestamp":1786978516925,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008903","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["PTH10529"],"award-info":[{"award-number":["PTH10529"]}],"id":[{"id":"10.13039\/100008903","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Oxidative stress may play critically important roles in the etiology of Parkinson's disease (PD). 6\u2010Hydroxydopamine (6\u2010OHDA) is a physiological neurotoxin reported to induce oxidative\u2010induced apoptosis of dopaminergic neurons in PD mice models. Valproic acid (VPA), a clinical mood stabilizer, is a HDAC inhibitor with neuroprotective capacities. In the study, we aim at examining the feasibility of VPA as a protector for dopaminergic neurons against damage from 6\u2010OHDA, and the intracellular mechanisms. The 6\u2010OHDA\u2010induced neurotoxicity to the human dopaminergic cell line SH\u2010SY5Y was applied for examining VPA protective effects. Pretreatment with VPA was able to improve cell viability and reduce 6\u2010OHDA\u2010induced reactive oxygen species. Furthermore, a significant suppression of apoptotic caspases including cleaved caspase\u20103, caspase\u20107, and caspase\u20109 was observed. The results also revealed VPA decreased the 6\u2010OHDA\u2010induced Bax\/Bcl2 ratio, as measured at protein level. These novel findings indicate that VPA may be capable of protecting the SH\u2010SY5Y dopaminergic neuronal cells from 6\u2010OHDA\u2010induced toxicity via the deceasing of apoptotic caspases (cleaved caspase\u20103, caspase\u20107, and caspase\u20109) and reducing of the Bax\/Bcl2 ratio. Very possibly, VPA could serve as not only a mood stabilizer but also a potential antidote for PD prevention.<\/jats:p>","DOI":"10.1002\/tox.22920","type":"journal-article","created":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T08:07:18Z","timestamp":1584086838000},"page":"840-848","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Protective effects of valproic acid on 6\u2010hydroxydopamine\u2010induced neuroinjury"],"prefix":"10.1002","volume":"35","author":[{"given":"Shih\u2010Wei","family":"Hsu","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences China Medical University  Taichung Taiwan"},{"name":"National Defense Medical Center  Taipei Taiwan"},{"name":"Taichung Armed Forces General Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Chen","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of 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