title: Alleviation of Oxidative Damage and Involvement of Nrf2-ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline.
abstract: The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats. The transient activation of Nrf2 in SE rats was enhanced by Ptx pretreatment, which was followed by the upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Ptx pretreatment to SE rats significantly suppressed the epileptic seizures, decreased the levels of lipid peroxide and malondialdehyde, and elevated the ratio of reduced glutathione/oxidized glutathione. Compared with intraperitoneal injection, intranasal Ptx delivery completely restored the visuospatial memory and the activity of mesodopaminergic system in SE rats. Intranasal administration of Ptx may hopefully become a noninvasive, painless, and easily administered option for epileptic patients.
authors.affiliation: Department of Neurobiology, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
authors.forename: Yunxiao
authors.identifier: 0000-0003-3021-8863
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Neurobiology, Hebei Medical University, Shijiazhuang, Hebei 050017, China; Department of Human Anatomy, Shijiazhuang Medical College, Shijiazhuang, Hebei 050599, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Neurobiology, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Human Anatomy, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei 050017, China.
authors.forename: Yakun
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Human Anatomy, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Human Anatomy, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
authors.forename: Huixian
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Neurobiology, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
authors.forename: Geming
authors.identifier: 0000-0003-2822-7576
authors.initials: G
authors.lastname: Shi
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology; D015153:Blotting, Western; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013226:Status Epilepticus / Q000188:drug therapy / Q000517:prevention & control
chemical_list: D000927:Anticonvulsants; D015259:Dopamine Agents; D051267:NF-E2-Related Factor 2; D010431:Pentoxifylline