Seizure-induced formation of isofurans: novel products of lipid peroxidation whose formation is positively modulated by oxygen tension.
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.
Patel
Manisha
M
Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. manisha.patel@uchsc.edu
Liang
Li-Ping
LP
Hou
Huagang
H
Williams
Benjamin B
BB
Kmiec
Maciej
M
Swartz
Harold M
HM
Fessel
Joshua P
JP
Roberts
L Jackson
LJ
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
D028441:F2-Isoprostanes; D005663:Furans; D007211:Indoles; D028421:Isoprostanes; D009942:Organometallic Compounds; C081756:lithium phthalocyanine; D010100:Oxygen; D007608:Kainic Acid