Mitochondrial complex I inhibition in cerebral cortex of immature rats following homocysteic acid-induced seizures
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
17270175
DOI
10.1016/j.expneurol.2006.12.010
PII: S0014-4886(06)00643-1
Knihovny.cz E-resources
- MeSH
- Aconitate Hydratase metabolism MeSH
- Analysis of Variance MeSH
- Antioxidants pharmacology MeSH
- Citrate (si)-Synthase metabolism MeSH
- Cyclic N-Oxides pharmacology MeSH
- Energy Metabolism drug effects MeSH
- Homocysteine analogs & derivatives MeSH
- Rats MeSH
- Drug Interactions MeSH
- Metalloporphyrins pharmacology MeSH
- Mitochondria drug effects MeSH
- Cerebral Cortex enzymology growth & development ultrastructure MeSH
- Animals, Newborn MeSH
- Lipid Peroxidation drug effects MeSH
- Rats, Wistar MeSH
- Electron Transport Complex I antagonists & inhibitors metabolism MeSH
- Spin Labels MeSH
- Oxygen Consumption drug effects MeSH
- Seizures chemically induced pathology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron(III) chloride MeSH Browser
- Aconitate Hydratase MeSH
- Antioxidants MeSH
- Citrate (si)-Synthase MeSH
- Cyclic N-Oxides MeSH
- homocysteic acid MeSH Browser
- Homocysteine MeSH
- Metalloporphyrins MeSH
- Electron Transport Complex I MeSH
- Spin Labels MeSH
- tempol MeSH Browser
The major finding of the present study concerns the marked decrease of respiratory chain complex I activity in the cerebral cortex of immature rats following seizures induced by bilateral intracerebroventricular infusion of dl-homocysteic acid (600 nmol/side). This decrease was already evident during the acute phase of seizures (60-90 min after infusion) and persisted for at least 20 h after the seizures. It was selective for complex I since activities of complex II and IV and citrate synthase remained unaffected. Inhibition of complex I activity was not associated with changes in complex I content. Based on enhanced lipoperoxidation and decreased aconitase activity, it can be postulated that oxidative modification is most likely responsible for the observed inhibition. Mitochondrial respiration, as well as cortical ATP levels remained in the control range, apparently due to excess capacity of the complex I documented by energy thresholds. On the other hand, the enhanced production of reactive oxygen species by inhibited complex I was observed in mitochondria from HCA-treated animals. The decrease of complex I activity was substantially attenuated when animals were treated with substances providing an anticonvulsant effect and also with selected free radical scavengers. We can assume that inhibition of complex I may elicit enhanced formation of reactive oxygen species and contribute thus to neuronal injury demonstrated in this model.
References provided by Crossref.org
Epilepsy Research in the Institute of Physiology of the Czech Academy of Sciences in Prague
Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature Rats
