title: Protective Effect of Dimethyl Fumarate on an Oxidative Stress Model Induced by Sodium Nitroprusside in Mice.
abstract: Recent reports have shown that dimethyl fumarate (DMF) prevents brain damage induced by intracerebral hemorrhage and this beneficial effect is mediated by the nuclear erythroid 2 p45-related factor-2-antioxidant response element (Nrf2-ARE) pathway. However, the downstream mechanism underlying the activation of the Nrf2-ARE pathway is unclear. Here, we investigated the protective effect of DMF using an in vivo model of oxidative stress induced by sodium nitroprusside (SNP) and rat primary striatal cultures. Oral administration of DMF prevented SNP-induced motor dysfunction. Pre-administration of DMF (60-200 mg/kg) for 24 h dose-dependently protected against brain damage induced by the striatal injection of SNP. Next, we investigated the protective effect and mechanism of DMF against oxidative stress using rat primary striatal cell cultures. Treatment of striatal cells with DMF (10 µM) markedly prevented hydrogen peroxide-induced cytotoxicity. The protective effect of DMF against oxidative stress in vitro was inhibited by zinc protoporphyrin IX, an inhibitor of heme oxygenase-1, but not by buthionine sulfoximine, an inhibitor of glutathione synthesis. These results suggest that the activation of heme oxygenase-1 plays an important role in the protective effect of DMF.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kume
authors.forename: Aya
authors.initials: A
authors.lastname: Suenaga
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Izumi
authors.forename: Akinori
authors.initials: A
authors.lastname: Akaike
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000069462:Dimethyl Fumarate / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D008297:Male; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009599:Nitroprusside / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D045442:Rotarod Performance Test
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D009599:Nitroprusside; D006861:Hydrogen Peroxide; D000069462:Dimethyl Fumarate