Seizure-induced formation of isofurans: novel products of lipid peroxidation whose formation is positively modulated by oxygen tension |
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| Authors: | Patel Manisha Liang Li-Ping Hou Huagang Williams Benjamin B Kmiec Maciej Swartz Harold M Fessel Joshua P Roberts L Jackson |
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| Institution: | Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, Colorado, USA;
Department of Radiology, Dartmouth Medical School, Hanover, New Hampshire, USA;
Departments of Pharmacology and Medicine, Vanderbilt University, Nashville, Tennessee, USA |
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| Abstract: | We have previously shown that seizures induce the formation of F2-isoprostanes (F2-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 F2-IsoPs. The present study determined seizure-induced formation of IsoFs and its relationship with cellular oxygen levels (pO2). Status epilepticus (SE) resulted in F2-IsoP and IsoF formation, with overlapping but distinct time courses in hippocampal subregions. IsoF, but not F2-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 F2-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. |
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| Keywords: | arachidonic acid kainic acid mitochondria oxidation seizures tissue oxygen |
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