title: Seizure-induced formation of isofurans: novel products of lipid peroxidation whose formation is positively modulated by oxygen tension.
abstract: We have previously shown that seizures induce the formation of F(2)-isoprostanes (F(2)-IsoPs), one of the most reliable indices of oxidative stress in vivo. Isofurans (IsoFs) are novel products of lipid peroxidation whose formation is favored by high oxygen tensions. In contrast, high oxygen tensions suppress the formation of F(2)-IsoPs. The present study determined seizure-induced formation of IsoFs and its relationship with cellular oxygen levels (pO2). Status epilepticus (SE) resulted in F(2)-IsoP and IsoF formation, with overlapping but distinct time courses in hippocampal subregions. IsoF, but not F(2)-IsoP formation coincided with mitochondrial oxidative stress. SE resulted in a transient decrease in hippocampal pO2 measured by in vivo electron paramagnetic resonance oximetry suggesting an early phase of seizure-induced hypoxia. Seizure-induced F(2)-IsoP formation coincided with the peak hypoxia phase, whereas IsoF formation coincided with the 'reoxygenation' phase. These results demonstrate seizure-induced increase in IsoF formation and its correlation with changes in hippocampal pO2 and mitochondrial dysfunction.
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. manisha.patel@uchsc.edu
authors.forename: Manisha
authors.initials: M
authors.lastname: Patel
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Liang
authors.forename: Huagang
authors.initials: H
authors.lastname: Hou
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Williams
authors.forename: Maciej
authors.initials: M
authors.lastname: Kmiec
authors.forename: Harold M
authors.initials: HM
authors.lastname: Swartz
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Fessel
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
mesh_terms: D031841:Aconitum / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D028441:F2-Isoprostanes / Q000378:metabolism; D005663:Furans / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007211:Indoles; D028421:Isoprostanes / Q000145:classification* / Q000378:metabolism*; D007608:Kainic Acid; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009942:Organometallic Compounds; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D028441:F2-Isoprostanes; D005663:Furans; D007211:Indoles; D028421:Isoprostanes; D009942:Organometallic Compounds; C081756:lithium phthalocyanine; D010100:Oxygen; D007608:Kainic Acid