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It is characterized biochemically by tissue sulfite accumulation. Patients present with seizures, progressive neurological damage, and basal ganglia abnormalities, the pathogenesis of which is not fully established. Treatment is supportive and largely ineffective. To address the pathophysiology of sulfite toxicity, we examined the effects of intrastriatal administration of sulfite in rats on antioxidant defenses, energy transfer, and mitogen\u2010activated protein kinases (MAPK) and apoptosis pathways in rat striatum. Sulfite administration decreased glutathione (GSH) concentration and glutathione peroxidase, glucose\u20106\u2010phosphate dehydrogenase, glutathione S\u2010transferase, and glutathione reductase activities in striatal tissue. Creatine kinase (CK) activity, a crucial enzyme for cell energy transfer, was also decreased by sulfite. Superoxide dismutase\u20101 (SOD1) and catalase (CAT) proteins were increased, while heme oxygenase\u20101 (HO\u20101) was decreased. Additionally, sulfite altered phosphorylation of MAPK by decreasing of p38 and increasing of ERK. Sulfite further augmented the content of GSK\u20103\u03b2, Bok, and cleaved caspase\u20103, indicating increased apoptosis. JP4\u2010039 is a mitochondrial\u2010targeted antioxidant that reaches higher intramitochondrial levels than other traditional antioxidants. Intraperitoneal injection of JP4\u2010039 before sulfite administration preserved activity of antioxidant enzymes and CK. It also prevented or attenuated alterations in SOD1, CAT, and HO\u20101 protein content, as well as changes in p38, ERK, and apoptosis markers. In sum, oxidative stress and apoptosis induced by sulfite injection are prevented by JP4\u2010039, identifying this molecule as a promising candidate for pharmacological treatment of SO\u2010deficient patients.<\/jats:p>","DOI":"10.1002\/jimd.12310","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T20:24:18Z","timestamp":1599164658000},"page":"481-491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The mitochondrial\u2010targeted reactive species scavenger <scp>JP4<\/scp>\u2010039 prevents sulfite\u2010induced alterations in antioxidant defenses, energy transfer, and cell death signaling in striatum of rats"],"prefix":"10.1002","volume":"44","author":[{"given":"N\u00edcolas Manzke","family":"Gl\u00e4nzel","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Universidade Federal do Rio Grande 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